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Top down proteomics in a TOF-TOF instrument was further explored by examining the fragmentation of multiply charged precursors ions generated by matrix-assisted laser desorption ionization. Evaluation of sample preparation conditions allowed selection of solvent/matrix conditions and sample deposition methods to produce sufficiently abundant doubly and triply charged precursor ions for subsequent CID experiments. As previously reported, preferential cleavage was observed at sites C-terminal to acidic residues and N-terminal to proline residues for all ions examined. An increase in nonpreferential fragmentation as well as additional low mass product ions was observed in the spectra from multiply charged precursor ions providing increased sequence coverage. This enhanced fragmentation from multiply charged precursor ions became increasingly important with increasing protein molecular weight and facilitates protein identification using database searching algorithms. The useable mass range for MALDI TOF-TOF analysis of intact proteins has been expanded to 18.2 kDa using this approach.
BACKGROUND - Preoperative chemotherapy and radiation therapy are often administered to patients with esophageal cancer. Despite an aging population, little data exist regarding feasibility of preoperative therapy in elderly patients.
METHODS - Between January 1997 and December 2002, 312 consecutive patients underwent esophagectomy for esophageal cancer at our institution. Outcomes of patients 70 years old, who underwent preoperative therapy (n = 35; group II), were compared with those of patients who did not (n = 39; group I) and with those of patients younger than 70 years old who received preoperative therapy (n = 165; group III).
RESULTS - The median age was 75 years old for group I and 72 years for group II (p < 0.001). The patients in group II were of more advanced clinical stage (p < 0.001). There were no differences in performance status, comorbidities, or preoperative symptoms between the two groups. Similar proportions of patients in the groups I and II underwent a transhiatal approach (52.5% vs 42.8%, p = not significant [NS]). Perioperative mortality for groups I and II was 0% and 3%, respectively (p = NS). Group II received more perioperative blood transfusions (71.4% vs 48.7%, p = 0.047). There were no differences in the rates of postoperative cardiac, pulmonary, neurologic, gastrointestinal, or anastomotic complications. Compared with group III, group II patients had higher rates of postoperative atrial arrhythmias (p = 0.013) and perioperative blood transfusions (p = 0.004).
CONCLUSIONS - Elderly patients receiving preoperative therapy for esophageal cancer do not have an increased incidence of major postoperative complications. Elderly patients receiving preoperative therapy are more likely to develop postoperative atrial arrhythmias and require transfusion than younger patients.
Liver and muscle metabolism were assessed in dogs adapted to long-term total parenteral (TPN) and enteral (TEN) nutrition. Studies were done in 13 conscious long-term catheterized dogs in which sampling (artery, portal and hepatic vein, and iliac vein), infusion catheters (inferior vena cava, duodenum), and transonic flow probes (hepatic artery, portal vein, and iliac artery) were implanted. Fourteen days after surgery dogs were grouped to receive TPN or TEN. After 5 days of TPN/TEN, substrate balances across the liver and limb were assessed. The liver was a marked net consumer of glucose in both groups (23.6 +/- 3.3 vs 22.6 +/- 2.8 micromol x kg(-1) x min(-1), TPN vs TEN) despite near normoglycemia (6.5 +/- 0.3 vs 6.7 +/- 0.2 mmol/L). Arterial insulin levels were higher during TEN (96 +/- 6 vs 144 +/- 30 pmol/L; p < .05). The majority (79 +/- 13 vs 76% +/- 7%) of the glucose taken up by the liver was released as lactate. Despite higher insulin levels during TEN the nonsplanchnic tissues consumed a lessor quantity of glucose (25.9 +/- 3.3 vs 16.1 +/- 3.9 micro x mol x kg(-1) x min(-1)). In summary, the liver undergoes a profound adaptation to TPN and TEN making it a major site of glucose uptake and conversion to lactate irrespective of the route of nutrient delivery. However, the insulin requirements are higher with TEN possibly secondary to impaired peripheral glucose removal.