Biomedical subjects

Y Shyr

Publications and source records attributed to Y Shyr.

At least 37 records · Page 2Linked to original sources

PubMed2001

Recombinant human growth hormone in patients with acute renal failure.

OBJECTIVE: The objective of this study is to determine the impact of recombinant human growth hormone (rhGH) on metabolic and nutritional parameters in malnourished patients with acute renal failure. DESIGN: The design is an open-labeled pilot trial examining the effects of rhGH administration in a small group of highly catabolic, malnourished patients with acute renal failure. Each patient served as his or her own control. SETTING: An intensive care unit in a tertiary care medical institution. PATIENTS: Five patients with established acute renal failure in a critical care unit. Entry criteria included clinical evidence of malnutrition: a serum albumin level of <3.2 g/dL, a prealbumin level of < or = 20 mg/dL, and an insulin-like growth factor IGF 1 level <200 ng/mL. The study consisted of 3 periods: phase I, 3 day baseline; phase II, 6 day treatment; and phase III, 3 day washout. During the entire study, blood and urine samples were obtained daily to calculate normalized protein catabolic rate, total nitrogen appearance rate (TNA), and nitrogen balance. Additional data were collected to measure metabolic and inflammatory parameters. INTERVENTION: The intervention consisted of administering 100 microg/kg/d of rhGH for 6 days. RESULTS: There were significant changes in TNA, normalized protein catabolic rate, and nitrogen balance during the 3 study phases. TNA decreased from 43.3 +/- 24.4 g/d in phase I, to 25.2 +/- 16.5 g/d during phase II (P <.001). There was a further decrease in TNA to 16.2 +/- 8.3 g/d during phase III (P <.001 v phase I). Nitrogen balance improved from - 31.8 +/- 21.4 g/d during phase I, to - 12.9 +/- 10.3 g/d during phase II (P <.001), and further improved to - 4.1 +/- 4.0 g/d in phase III (P <.001 v phase I). Significant changes were also noted in levels of blood urea nitrogen, phosphorous, serum growth hormone, IGF-1, and serum leptin levels after growth hormone administration. A statistically significant increase in serum albumin was noted in phase III (3.1 g/dL) versus phase I (2.7 +/- 0.7 g/dL). CONCLUSIONS: Administration of rhGH to critically ill patients with acute renal failure resulted in improvements in negative nitrogen balance and a significant decrease in total nitrogen appearance rate. These changes corresponded to increases in serum growth hormone, IGF-1, IGF-1 binding protein 3, and leptin levels after growth hormone administration.

Acute Kidney Injury↗

PubMed2001

Health related quality of life assessment after radical prostatectomy in men with prostate specific antigen only recurrence.

PURPOSE: The health related quality of life assessment is becoming increasingly important among patients with prostate cancer. Meanwhile, treatment of patients with increasing prostate specific antigen (PSA) after radical retropubic prostatectomy remains controversial. We attempt to define the impact of PSA recurrence on the health related quality of life of patients after radical retropubic prostatectomy. MATERIALS AND METHODS: Of 604 consecutive patients who underwent radical retropubic prostatectomy between March 1991 and September 1998, 510 (84%) were available for followup. Each patient was mailed the RAND 36-Item Health Survey and University of California, Los Angeles, Prostate Cancer Index questionnaire. A total of 348 (70%) questionnaires were returned. Health related quality of life scores were then compared between patients with and without PSA recurrence. A multivariate analysis was also performed to elucidate further the cause of differences between the groups. RESULTS: Overall, 88 (25%) patients had PSA recurrence. In regard to health related quality of life there were small (less than 10%) but statistically significant differences in 2 of 4 physical health domains (RAND 36-Item Health Survey). There was a significant decrease in only 1 category of the mental health domain for patients with PSA recurrence. Only sexual function was statistically lower on the University of California, Los Angeles, Prostate Cancer Index. This result reflects the lower incidence of nerve sparing in these patients, as confirmed by the multivariate analysis. Overall patient satisfaction was similar between those with and without PSA recurrence (76% and 79%, respectively). CONCLUSIONS: Our study demonstrates small health related quality of life differences in patients with biochemical PSA recurrence versus those without. These findings provide a baseline assessment of general and disease specific health related quality of life domains among these patients. Future studies should focus on differences in the measure of cancer anxiety before and after administration of adjuvant therapy in these asymptomatic patients.

Follow-Up Studies↗

PubMed2000

Targeting and therapy of carcinoembryonic antigen-expressing tumors in transgenic mice with an antibody-interleukin 2 fusion protein.

The purpose of this study was to engineer a bivalent single-chain anticarcinoembryonic antigen (CEA) antibody and an interleukin 2 (IL-2) fusion protein derivative for selective tumor targeting of cytokines. The variable domains of a high affinity anti-CEA antibody, T84.66, were used to form a single-gene-encoded antibody [single-chain variable fragment joined to the crystallizable fragment, Fc (scFvFc)]. The fusion protein (scFvFc.IL-2) consisted of mouse IL-2-fused to the COOH-terminal end of the scFvFc. The engineered proteins were assembled as complete molecules and were similar to the intact anti-CEA monoclonal antibody (Mab) in antigen-binding properties. Based on IL-2 content of the fusion protein, its ability to support proliferation of CTLL-2 cells was identical with that of IL-2. Despite a molecular size similar to that of the intact Mab, the blood clearance of the fusion protein was markedly faster than that of the intact Mab or scFvFc. Incubation of radiolabeled scFvFc.IL-2 but not the intact or scFvFc antibodies in mouse serum was accompanied by the appearance of complexes, suggesting that the latter may contribute to the accelerated clearance of the fusion protein. Biodistribution and tumor targeting studies were carried out in CEA-transgenic mice bearing CEA-positive murine tumors as well as the antigen-negative parental tumor. The bivalent anti-CEA scFvFc had tumor localization properties similar to those of the intact Mab. Although fusion of IL-2 to the COOH-terminal end of the bivalent scFvFc altered its pharmacokinetic properties, the fusion antibody was able to target tumors specifically. Maximum uptake of the intact Mab, scFvFc, and scFvFc.IL-2 in CEA-positive tumors was 29.3 +/- 5.0, 19.5 +/- 2.1, and 6.6 +/- 0.9% injected dose/g, respectively. Maximum tumor localization ratios (CEA-positive/CEA-negative tumor) were similar for all three antibody types (4.6-6.0), demonstrating the antigen specificity of the tumor targeting. Significant antigen-specific targeting to CEA-positive normal tissues of transgenic mice was not observed. Although the tumor-targeting properties of the fusion protein were low, the growth of CEA-expressing (P = 0.01) but not antigen-irrelevant (P = 0.22) syngeneic tumor cells was inhibited after treatment of transgenic mice with the anti-CEA-IL-2 antibody. Therapy of CEA-expressing tumors was improved after i.v. administration of the fusion protein (P = 0.0001). These studies indicate that anti-CEA antibody-directed cytokine targeting may offer an effective treatment for CEA-expressing carcinomas. The availability of an immunocompetent CEA transgenic mouse model will also help to determine the immunotherapeutic properties of these fusion proteins.

Animals↗

PubMed2000

A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study).

PURPOSE: We conducted a prospective phase II study to determine the response rate, toxicity, and survival rate of concurrent weekly paclitaxel, carboplatin, and hyperfractionated radiation therapy (paclitaxel/carboplatin/HFX RT) followed by 2 cycles of paclitaxel and carboplatin for locally advanced unresectable non-small cell lung cancer (NSCLC). The weekly paclitaxel and carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. METHODS AND MATERIALS: Forty-three patients with unresectable stage IIIA and IIIB NSCLC from the Vanderbilt Cancer Center and Affiliate Network (VCCAN) institutions were entered onto the study from June 1996 until May 1997. Weekly intravenous (IV) paclitaxel (50 mg/m(2)/l-hour) and weekly carboplatin (AUC 2) plus concurrent hyperfractionated chest RT (1.2 Gy/BID/69.6 Gy) were delivered for 6 weeks followed by 2 cycles of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). RESULTS: Forty-two patients were evaluable for response and toxicities. Three patients achieved a complete response (7.2%) and 30 patients achieved a partial response (71.4%), for an overall response rate of 78.6% [95% C.I. (66.2%-91.0%)]. The 1- and 2-year overall and progression-free survival rates of all 43 patients were 61.6% and 35% respectively, with a median survival time of 14.3 months. The median follow-up time was 14 months. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (26%). There was an incidence of 7% grade 3 and 9.5% grade 4 pulmonary toxicities. CONCLUSIONS: Weekly paclitaxel, carboplatin, plus concurrent hyperfractionated RT is a well-tolerated outpatient regimen. The response rate from this regimen is encouraging and appears to be at least equivalent to the more toxic chemoradiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/carboplatin/HFX RT in a phase III study.

Adenocarcinoma↗

PubMed2000

Patterns of practice survey for nonsmall cell lung carcinoma in the U.S.

BACKGROUND: Nonsmall cell lung carcinoma comprises approximately 75% of all lung carcinoma cases in the U.S. Newly evolving strategies have created considerable controversy regarding the optimal treatment for patients diagnosed with this disease. METHODS: A 17-item survey was designed to collect demographic data and information regarding practice patterns for nonsmall cell lung carcinoma, including patient assessment, treatment approaches, and roles of chemotherapy and radiotherapy. Surveys were mailed in the summer of 1997 to approximately 9200 oncologists of all types throughout the U.S. Practice settings included private office, private hospital, academic, university-affiliated office, government, and Veterans Administration institutions. RESULTS: Approximately 10% of the oncologists responded (n = 979), including 499 medical oncologists (51%), 464 radiation oncologists (47%), and 16 others (2%). For the adjuvant treatment of surgically resected N1-2 disease, combined modality treatment was preferred over radiation therapy alone by medical oncologists (48% vs. 16%; P<0.001) and radiation therapy alone was preferred over combined modality treatment by radiation oncologists (55% vs. 38%; P<0.001). The combination of paclitaxel and carboplatin was the preferred first-line regimen for all stages of nonsmall cell lung carcinoma by the majority of medical oncologists (55%), whereas the majority of radiation oncologists (58%) chose the combination of etoposide and platinum. With regard to the optimal combined modality approach, respondents were divided evenly between concurrent chemoradiotherapy (34%) and sequential chemoradiotherapy (31%). Overall, respondents reported basing treatment decisions largely on published literature (55%) compared with personal experience (19%), seminars and colleagues (16%), and clinical trial availability (10%) (P<0.001). CONCLUSIONS: This survey confirms many differences in practice patterns among medical oncologists and radiation oncologists in the treatment of patients with nonsmall cell lung carcinoma and suggests the need for the multidisciplinary management of this entity. In addition, the current study demonstrates that reliance on the medical literature as a basis for treatment steadily declines the longer the physician has been in practice.

Analysis of Variance↗

PubMed2000

Experimental study of mortality and morbidity of contrast media and standardized fecal dose in the peritoneal cavity.

BACKGROUND: The use of radiographic contrast media in the setting of possible bowel ischemia and potential perforation is known to be associated with increased clinical risk. However, there is a lack of controlled studies using a standard native fecal load to define and compare the intrinsic mortality and morbidity among options of contrast media currently available to the radiologist. We have compared the mortality and gross and histopathologic morbidity of a standard intraperitoneal native fecal dose in the guinea pig, using barium, two iodinated media, saline and air. MATERIALS AND METHODS: The study was performed on adult Hartley guinea pigs. A standard native fecal solution with a colony count of 10(8) aerobes and 2 x 10(7) anaerobes was prepared, and the LD50 of intraperitoneal injection of the solution was determined. The standard solution at the LD50 dose was then used to compare the mortality and morbidity when commercial barium sulfate (18% w/v), Conray 30 (iothalamate meglumine 30%), 1:1 dilution of Conray 30 with sterile water, termed Conray "15" (iothalamate meglumine 15%), saline and air, were added to the intraperitoneal injection of the fecal solution in five groups of 20 animals each. Mortality and acute (96 h) and chronic (30 days) gross and histopathology were assessed and graded according to a standard system and analyzed statistically. RESULTS: Barium was significantly more deleterious than the dilute water-soluble iodinated media, saline and air. Mortality occurred within 24 h in the barium group and within the initial 48 h in all groups as follows: barium 19/20 (95%); Conray 30 16/20 (80%); Conray "15" 7/20 (35%); saline 0; air 0. Acute gross and histopathology showed extensive grade 4 lesions in 19/19 barium animals; less severe lesions were present in a lesser percentage of the animals in the other four groups. Entirely chronic lesions were present only in the single surviving barium animal and were non-significant (< 400 microns) or absent in the other four groups. CONCLUSIONS: In our study, barium incurred the most significant deleterious short and long-term effects in the setting of fecal peritonitis. Dilute water-soluble media offer a much greater margin of safety. Saline under sonographic guidance is less deleterious than any of the positive radiographic contrast media. However, in our study, air was the safest contrast medium in the setting of peritoneal soiling.

Animals↗

PubMed2000

Induction of cytotoxic T cells and their antitumor activity in mice transgenic for carcinoembryonic antigen.

In order to develop immunotherapy strategies that are based on eliciting immune responsiveness to the self-antigen, human carcinoembryonic antigen (CEA), we examined whether cytotoxic T lymphocyte (CTL) activity against CEA could be elicited in CEA-transgenic and nontransgenic mice. CEA-transgenic [C57BL/ 6-TGN(CEAGe)18FJP] and nontransgenic mice were primed with CEA-transfected syngeneic fibroblasts in combination with Corynebacterium parvum. Spleen cells from immunized mice were cultured with irradiated syngeneic MC-38 colon carcinoma cells transfected with CEA (MC-38.CEA) as stimulators prior to the measurement of CTL activity. Primed nontransgenic spleen cells showed augmented CTL activity against MC-38.CEA cells as compared with control parental MC-38 cells, nontransfected or transfected with vector only. Moreover, primed CEA transgenic spleen cells showed augmented CTL activity against MC-38.CEA cells that was similar to that observed in nontransgenic mice. All CTL clones derived from either transgenic or nontransgenic mice showed cross-reactivity with MC-38 cells expressing the CEA-related antigen, nonspecific cross-reacting antigen, but not biliary glycoprotein. CEA-specific CTL clones were not identified. Adoptive transfer of cloned CTL resulted in inhibition of MC-38.CEA but not MC-38.BGP tumor growth. Tumor cures were elicited in mice treated with a combination of cloned CTL and cyclophosphamide. Histopathological examination of CEA-expressing colons from either immunized mice or recipients of cloned CTL did not reveal any autoimmune reactions. These studies demonstrate that CTL recognizing cross-reactive class I epitopes on the CEA molecule can be induced in transgenic mice. The expression of these epitopes on tumor cells creates effective targets for CTL in vivo without inducing adverse reactions in CEA-expressing normal tissues. Since anti-CEA CTL have been generated in humans, CEA-transgenic mice may be a useful model to study vaccines that are based on CTL effector mechanisms.

Animals↗

PubMed2000

Enhanced expression of cyclooxygenase-2 in high grade human transitional cell bladder carcinomas.

Studies in human and animal models have shown that cyclooxygenase (COX)-2 is up-regulated in several epithelial carcinomas including colon, breast, and lung. To elucidate the possible involvement of COX-2 in human bladder cancer we examined the expression of COX isoforms in benign tissue and in bladder carcinoma specimens. Paraffin embedded tissues from 75 patients with urothelial carcinomas were immunostained with specific antibodies raised against COX-1 and COX-2. COX-1 expression was detected in smooth muscle cells in both benign and malignant bladders. COX-2 immunoreactivity was absent in benign tissue and in specimens with low-grade urothelial carcinoma (0/23). In contrast, expression of COX-2 was detected in malignant epithelial cells in 38% (17/47) of specimens with high-grade urothelial carcinomas. Expression of COX-2 in high-grade bladder cancer was confirmed by radioactive in situ hybridization using a COX-2-selective riboprobe. Both immunohistochemistry and in situ hybridization showed COX-2 expression in a small subset of malignant cells. COX-2 mRNA was also expressed in three out of seven malignant urothelial cell lines. These data demonstrate elevated expression of COX-2 in a high percentage of high-grade bladder carcinomas, suggesting a possible role of COX-2 in the progression of bladder urothelial carcinoma and supporting its potential as a therapeutic target in human bladder carcinoma.

Carcinoma, Transitional Cell↗

PubMed2000

Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, possibly related to abnormal brain-gut communication. Positron emission tomography imaging has suggested specific central nervous system (CNS) abnormalities in visceral pain processing in IBS. This study aimed to determine (1) if functional magnetic resonance imaging (fMRI) detects CNS activity during painful and nonpainful visceral stimulation; and (2) if CNS pain centers in IBS respond abnormally. METHODS: fMRI was performed during nonpainful and painful rectal distention in 18 patients with IBS and 16 controls. RESULTS: Rectal stimulation increased the activity of anterior cingulate (33/34), prefrontal (32/34), insular cortices (33/34), and thalamus (32/34) in most subjects. In IBS subjects, but not controls, pain led to greater activation of the anterior cingulate cortex (ACC) than did nonpainful stimuli. IBS patients had a greater number of pixels activated in the ACC and reported greater intensity of pain at 55-mm Hg distention than controls. CONCLUSIONS: IBS patients activate the ACC, a critical CNS pain center, to a greater extent than controls in response to a painful rectal stimulus. Contrary to previous reports, these data suggest heightened pain sensitivity of the brain-gut axis in IBS, with a normal pattern of activation.

Adult↗

PubMed2000

Preemptive gastrointestinal tract management reduces aspiration and respiratory failure after thoracic operations.

OBJECTIVES: Respiratory failure is the major mode of death after general thoracic operations. However, respiratory failure may develop from two very different mechanisms: aspiration, often caused by ileus, and pneumonia, which often results from poor pain control. Epidural catheters help control pain and prevent pneumonia but contribute to ileus and may increase aspiration. We report a decrease in the incidence of aspiration after changing postoperative care to include gastrointestinal tract management. METHODS: All patients undergoing elective thoracotomy by a single surgeon were evaluated for hospital mortality and morbidity. For the first 21 months, patients did not receive an intraoperative nasogastric tube and were prescribed an "advance as tolerated" diet after the operation (n = 125). For the second period, nasogastric tubes were placed intraoperatively and patients received nothing by mouth the day of operation, clear liquids the first day, and a regular diet the second day (n = 153). Pneumonia was considered to have developed if infiltrates developed in a single lobe or two adjoining lobes and culture of the sputa grew a dominant organism. Patients were considered to have aspirated if diffuse infiltrates developed or cultures grew multiple organisms. Significance of results was determined by chi(2) testing. RESULTS: A total of 278 patients underwent elective lung resection over a 3(1/2)-year period, 125 with ad libitum dietary management and 153 with intensive management of the gastrointestinal tract. Six patients (4.84%) aspirated before the institution of gastrointestinal tract management, whereas none (0.0%) aspirated after the change. This difference was significant (P =.01). Respiratory mortality was eliminated in the group with gastrointestinal tract management (P =.04). CONCLUSIONS: Aspiration and its subsequent respiratory failure and mortality can be decreased with preemptive gastrointestinal tract management.

Diet↗

PubMed2000

Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver.

Factors associated with the development of fibrosis in nonalcoholic steatohepatitis (NASH) are largely unknown, although an association with increased hepatic iron has been suggested. Hepatic stellate cells are the principal collagen-producing cells in many liver diseases and when activated express alpha-smooth muscle actin (alpha-SMA). Hepatic stellate cell activation and association with fibrosis, necroinflammatory activity, steatosis, and stainable iron in 60 cases of NASH and 16 cases of steatosis were evaluated. All 76 patients were obese or had other risk factors for NASH. All biopsy specimens were stained for alpha-smooth muscle actin to evaluate the pattern of hepatic stellate cell activation and were evaluated for inflammatory activity (0 to 3), fibrosis (0 to 4), and stainable iron stores (0 to 4). The zonal location of activated stellate cells was recorded, and the degree of activation was graded as high-grade or low-grade based on the percentage of lobular alpha-SMA+ cells. Activated stellate cells were identified in the hepatic lobule in 74 of 76 biopsy specimens and graded as low-grade in 26 and high-grade in 48. Zone 3 was involved in 72 of 74 positive cases, and in 33 cases, the activated stellate cells were preferentially located in zone 3. The degree of stellate cell activation correlated with fibrosis but not with inflammatory activity, severity of steatosis, or stainable iron. In most cases, the degree of stellate cell activation paralleled the degree of hepatic fibrosis, but in 25 cases, the degree of hepatic stellate cell activation was greater than expected, raising the question of whether such patients are at risk for disease progression.

Actins↗

PubMed2000

Serum transferrin and serum prealbumin are early predictors of serum albumin in chronic hemodialysis patients.

Protein-calorie malnutrition is a known risk factor for increased morbidity and mortality in maintenance hemodialysis patients (MHD). Serum albumin is the most commonly measured nutritional index in MHD patients because of its easy routine availability and association with outcomes of interest. However, its long half-life of approximately 20 days makes it a late index of nutritional status, and its exclusive use may delay implementation of appropriate nutritional interventions. Serum prealbumin and transferrin have been proposed as earlier nutritional markers. However, the temporal associations among these indices and serum albumin have not been well documented. To assess the ability of serum prealbumin and serum transferrin to predict changes in serum albumin over time, we prospectively analyzed these parameters in 105 MHD patients every month for 6 consecutive months. The mixed model analysis showed that early changes in either serum transferrin or prealbumin predicted and were significantly associated with changes in serum albumin (P<.0001). Using a prototype equation, a change of 0.12 g/dL in serum albumin concentration can be predicted by a 10% change in the same direction of serum transferrin and prealbumin. We conclude that clinically significant changes in albumin can be reliably predicted by earlier changes in serum transferrin and prealbumin.

Adult↗

PubMed2000

Effect of immediate weightbearing on plated fractures of the humeral shaft.

BACKGROUND: This study evaluated the effect of immediate weightbearing on fractures of the humeral shaft treated with dynamic compression plates. METHODS: Eighty-three fractures met the inclusion criteria. The weightbearing status of the humerus was based on associated injuries and not the fracture pattern. There were no differences between the weightbearing and nonweightbearing groups in patient or fracture demographics. RESULTS: Ninety-four percent of the fractures healed after the initial operation. Two in the nonweightbearing group and three in the weightbearing group required a second operation to achieve union. Alignment did not differ between the two groups. Immediate full weight. bearing had no effect on the union or malunion rate. CONCLUSION: When indicated, open reduction and internal fixation of the diaphysis of the humerus, followed by immediate weightbearing through the involved humerus, is a safe and efficacious procedure.

Adolescent↗

PubMed2000

Registration of physical space to laparoscopic image space for use in minimally invasive hepatic surgery.

While laparoscopes are used for numerous minimally invasive (MI) procedures, MI liver resection and ablative surgery is infrequently performed. The paucity of cases is due to the restriction of the field of view by the laparoscope and the difficulty in determining tumor location and margins under video guidance. By merging MI surgery with interactive, image-guided surgery (IIGS), we hope to overcome localization difficulties present in laparoscopic liver procedures. One key component of any IIGS system is the development of accurate registration techniques to map image space to physical or patient space. This manuscript focuses on the accuracy and analysis of the direct linear transformation (DLT) method to register physical space with laparoscopic image space on both distorted and distortion-corrected video images. Experiments were conducted on a liver-sized plastic phantom affixed with 20 markers at various depths. After localizing the points in both physical and laparoscopic image space, registration accuracy was assessed for different combinations and numbers of control points (n) to determine the quantity necessary to develop a robust registration matrix. For n = 11, average target registration error (TRE) was 0.70 +/- 0.20 mm. We also studied the effects of distortion correction on registration accuracy. For the particular distortion correction method and laparoscope used in our experiments, there was no statistical significance between physical to image registration error for distorted and corrected images. In cases where a minimum number of control points (n = 6) are acquired, the DLT is often not stable and the mathematical process can lead to high TRE values. Mathematical filters developed through the analysis of the DLT were used to prospectively eliminate outlier cases where the TRE was high. For n = 6, prefilter average TRE was 17.4 +/- 153 mm for all trials; when the filters were applied, average TRE decreased to 1.64 +/- 1.10 mm for the remaining trials.

Humans↗

PubMed2000

Appendicolith revealed on CT in children with suspected appendicitis: how specific is it in the diagnosis of appendicitis?

OBJECTIVE: The purpose of this study was to determine the sensitivity, specificity, and positive and negative predictive values of a diagnosis of appendicitis when CT without enteric contrast material reveals an appendicolith in children with suspected appendicitis. MATERIALS AND METHODS: A retrospective review of children who underwent abdominal CT for suspected appendicitis over a 25-month period was performed to identify patients with an appendicolith. An age-matched group of patients examined for trauma served as controls. RESULTS: CT was performed in 104 children. Appendicitis was present in 60 (58%) of 104 children; 39 (65%) of 60 had an appendicolith. Appendicitis was not present in 44 (42%) of 104; six (14%) of 44 had an appendicolith. An appendicolith detected on CT had a sensitivity of 65% and a specificity of 86% for the radiologist diagnosing appendicitis. An appendicolith had a positive predictive value of 74% and a negative predictive value of 26%. Among the control population, two (3%) of 74 children had an appendicolith. This number was statistically significant compared with children in the study group with an appendicolith and abdominal pain, but without appendicitis (p = 0.02). CONCLUSION: Although an appendicolith is significantly associated with appendicitis, the detection of an isolated appendicolith on CT is not sufficiently specific to be the sole basis for the diagnosis of acute appendicitis.

Adolescent↗

PubMed2000

A pilot study of neoadjuvant paclitaxel and radiation with correlative molecular studies in stage II/III breast cancer.

A commonly used approach to the management of locally advanced breast cancer currently involves neoadjuvant chemotherapy, followed by surgery and radiation. Earlier neoadjuvant regimens had utilized doxorubicin, making concurrent treatment with radiation less desirable given dose-limiting normal tissue toxicities. With the development of paclitaxel, we can now reconsider the use of concurrent chemoradiation in the treatment of breast cancer. Although paclitaxel is a known radiation sensitizer, its precise mechanism of action is still unclear. One of its proposed mechanisms is that it binds tubulin and induces an M-phase arrest. As cells in M-phase are very sensitive to radiation, it thereby increases radiation sensitivity. The ability to predict tumor response for individual patients would allow us to tailor subsequent therapy for the individual patient. This study is designed to evaluate if paclitaxel's effects on the cell cycle of an individual patient can predict the responsiveness of that patient's tumor to paclitaxel and radiation. Patients will be treated with 3 cycles of paclitaxel followed by concurrent paclitaxel and radiation prior to definitive surgery.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Paclitaxel, 5-fluorouracil, and leucovorin (TFL) in the treatment of metastatic breast cancer.

To assess the activity of paclitaxel in combination with 5-fluorouracil (5-FU) and leucovorin in breast cancer, a phase II trial was conducted in women with metastatic disease. Toxicity, response rate, median survival, median duration of response, and median time to disease progression were measured. Between January 1994 and May 1996, 47 patients with metastatic breast cancer and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 who had previously been treated with chemotherapy received 175 mg/m2 paclitaxel over 3 hours on day 1. After paclitaxel administration, 300 mg intravenous (i.v.) leucovorin over 30 minutes was administered followed by 350 mg/m2 i.v. push 5-FU. Both 5-FU and leucovorin were given on days 1-3. Treatment was repeated every 28 days for a minimum of 6 cycles per patient. Two (4%) patients had a complete response and 21 (45%) patients had a partial response for an overall response rate of 49% (95% confidence interval: 35%-63%). The median survival was 17.7 months, median duration of response was 8.6 months, and median time to disease progression was 6.3 months. There was no statistical difference in survival or time to progression between anthracycline-naive, anthracycline-sensitive, and anthracycline-resistant patients. Nine (19%) patients had grade 3 or 4 neutropenia, and no patient required blood or platelet transfusion. The most frequently observed nonhematologic toxicities were arthralgia and myalgia. Pharmacokinetic data were obtained on 19 patients. Responders had higher peak plasma concentrations of paclitaxel than nonresponders (4.46 vs. 2.9 micrograms/mL; P = 0.02). Paclitaxel/5-fluorouracil/leucovorin is an active, well-tolerated regimen for patients with metastatic breast cancer.

Adult↗

PubMed2000

A phase I trial of outpatient weekly docetaxel and concurrent radiation therapy for stage III unresectable non small-cell lung cancer: a Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial.

Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical studies, probably due to its role as a cell cycle synchronizer for the G2/M radiosensitive phase of the cell cycle. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of docetaxel with concurrent thoracic radiation therapy (TRT) to patients with unresectable stage III non small-cell lung cancer (NSCLC). Fifteen patients were entered into this study. Docetaxel was administered as a 1-hour intravenous (I.V.) infusion, repeated every week for 6 weeks with starting dose of 20 mg/m2. Doses were escalated in 10 mg/m2 increments in successive cohorts of three new patients, if tolerated. Unacceptable toxicity was defined as grade = 3 nonhematologic or hematologic toxicity according to Eastern Cooperative Oncology Group (ECOG) toxicity criteria. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). At the first dose level (20 mg/m2/week), one patient developed grade 4 hyperglycemia and accrual was expanded to five patients. At the second level (30 mg/m2/week), two out of six patients developed grade 3 esophagitis. At the third level (40 mg/m2/week), two out of four patients developed grade 3 esophagitis and one patient developed grade 3 pulmonary toxicity. The weekly docetaxel MTD with concurrent radiation therapy (RT) was found to be 30 mg/m2. The DLT was esophagitis and pulmonary toxicity. Other toxicities encountered included skin reaction, nausea and vomiting, as well as diarrhea. Additionally, there were no treatment-related mortalities or late-occurring toxicities. Esophagitis was the principal DLT of concurrent weekly docetaxel and thoracic radiation in the outpatient setting. The MTD of concurrent weekly docetaxel with TRT is 30 mg/m2 weekly for 6 weeks. This study is still open to accrual with weekly docetaxel and TRT in locally advanced NSCLC patients.

Journal Article↗