A hospital and home-based exercise program to address functional decline in people following allogeneic stem cell transplantation.

PURPOSE: The aims of this study are to investigate the feasibility of an exercise program commencing 60 days following allogeneic stem cell transplantation (alloSCT), to investigate changes in physical function and health-related quality of life (HRQoL) in patients from pre- to post-alloSCT and to explore changes in patient outcomes before and after the program. METHODS: This study is a single site, prospective case series including 43 adults undergoing alloSCT. The intervention was an 8-week outpatient and home-based exercise and education program. Outcomes included feasibility (consent, attendance, compliance and completion rates), functional exercise capacity (incremental shuttle walk test), muscle strength (hand-held dynamometry), self-efficacy for physical activity (Physical Activity Assessment Inventory) and HRQoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplant). Outcomes were measured pre-alloSCT, 60 days post-alloSCT (pre-intervention) and 100 days post-alloSCT (post-intervention). RESULTS: The consent rate was 93%. From baseline to 60 days post-alloSCT, there was significant decline in functional exercise capacity (mean difference 224 m, 95% CI 153-295, p < 0.0005), self-efficacy for physical activity (294 points, 95% CI 136-452, p = 0.001) and HRQoL (15 points, 95% CI 8-21, p < 0.0005). Ten participants did not commence the exercise program due to death (n = 5), illness (n = 1) or cancellation of alloSCT (n = 4). The intervention was feasible in those not affected by major medical complications or death. No adverse events occurred. From pre- to post-intervention, there was significant improvement in functional exercise capacity (p = 0.001) and HRQoL (p = 0.001). CONCLUSIONS: AlloSCT results in significant decline in functional exercise capacity, self-efficacy for physical activity and HRQoL, which may be improved through an exercise program. This pilot demonstrated safety, feasibility and high patient interest. Further randomised research is required.

[Surgical methods used in the treatment of local gingival recession]. / Khirurgicheskie metody, ispol'zuemye pri ustranenii lokal'noi retsesii desny.

Surgical methods used for repair of gingival recession are reviewed. Modern methods and means of plastic periodontal surgery solve many esthetic problems. The prognosis of the results of gingival plasty in cases of recession of different classes is now becoming more and more favorable. The method of purposeful tissue regeneration is a good supplement to surgical treatment of gingival recession.

A high-throughput assay for rat liver golgi and Saccharomyces cerevisiae-expressed murine CMP-N-acetylneuraminic acid transport proteins.

Rat liver Golgi and Saccharomyces cerevisiae-expressed CMP-Neu5Ac transport protein were reconstituted in phosphatidylcholine liposomes and transport of CMP-Neu5Ac into these proteoliposomes was determined. The separation of transported substrate from free substrate was performed using Multiscreen minicolumns loaded with Sephadex G-50 resin (fine). The CMP-Neu5Ac transport characteristics of the rat liver Golgi and S. cerevisiae-expressed transporters, determined using this separation system, were very similar to those previously reported. Inhibition studies, utilizing the above procedure, revealed that the main structural features required for recognition of glycosyl nucleosides by the rat liver Golgi CMP-Neu5Ac transport protein were the nature of the nucleoside base and the anomeric configuration of the associated carbohydrate. In general, pyrimidine-based glycosyl nucleosides were found to inhibit transport to a far greater extent than purine-based glycosyl nucleosides, an observation that is in good agreement with previous reports. These results indicate that the reconstitution procedure, in conjunction with Multiscreen minicolumns, is an effective high-throughput method for the determination of CMP-Neu5Ac transport.

Production of an enterotoxin by a gastro-enteritis-associated Aeromonas strain.

The potential of motile Aeromonas species to cause human gastrointestinal infections has been recognised recently. Considerable worldwide epidemiological, microbiological and clinical investigations have shown that some strains of the different motile aeromonads are of increasing enteropathogenic significance, especially in children, the elderly and in immunocompromised individuals. Some of the diarrhoeal symptoms of Aeromonas-associated gastro-enteritis have been attributed to enterotoxins. In this study, 15 Aeromonas isolates from clinical and non-clinical sources, representing the three motile aeromonads commonly associated with gastro-enteritis (A. caviae, A. hydrophila and A. veronii biovar sobria), were tested for their ability to cause fluid accumulation in infant mice by the suckling mouse technique. Eight isolates were found to produce enterotoxin. Of these, an A. veronii biovar sobria strain (AS15), isolated from lamb kidney, was found to produce the highest enterotoxin score. An enterotoxin of c. 40 kDa produced by A. veronii biovar sobria AS15 was purified by Sephacryl S-100 gel filtration and high-performance liquid chromatography. This enterotoxin caused marked fluid accumulation in infant mice by the suckling mouse technique. The purified enterotoxin cross-reacted with cholera toxin antibodies and was readily inactivated by heating at 56 degrees C for 10 min. The production of a 'cholera-like' enterotoxin by Aeromonas isolates from samples of animal origin suggests that these organisms could be of public health significance in food products.

Preliminary 1H NMR investigation of sialic acid transfer by the trans-sialidase from Trypanosoma cruzi.

1H NMR spectroscopy has been used to investigate the transfer of sialic acid from sialic acid donor molecules to acceptor molecules using the trans-sialidase from Typanosoma cruzi. It is clearly demonstrated that NMR spectroscopy is an efficient and powerful means of monitoring the trans-sialidase promoted transfer of sialic acid from donor to acceptor.

Synthesis of delta4-beta-D-glucopyranosiduronic acids as mimetics of 2,3-unsaturated sialic acids for sialidase inhibition.

Mimetics of Neu5Ac2en and KDN2en, based on delta4-beta-delta-glucopyranosiduronic acids, have been synthesised. The Neu5Ac2en mimetic 5 showed inhibition of both bacterial and viral sialidases, with inhibition of the viral sialidase being comparable to that of Neu5Ac2en itself.

The synthesis and evaluation of novel sialic acid analogues bound to matrices for the purification of sialic acid-recognising proteins.

A novel N-acetylneuraminic acid analogue, 2-S-(5'-aminopentyl) 5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-2- nonulopyranosidonic acid, as well as the thiosialoside 2-S-(2'-aminoethyl) 5-acetamido-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-2- nonulopyranosidonic acid, have been synthesised and successfully coupled to CNBr-activated Sepharose 4B through the terminal amino group. The resultant affinity resins have proved efficient in purifying a number of sialic acid-recognising proteins such as Vibrio cholerae sialidase, sialidase-L from leech, trans-sialidase from Trypanosoma cruzi, and sialyltransferases from rat liver, all in high yield.

Peripheral edema after esophagectomy.

Patients who have undergone major surgery such as esophagectomy may develop peripheral edema in the immediate postoperative period, the cause of which is not fully understood. The purpose of this study was therefore to determine the mechanism of this phenomenon. Finger edema was measured as a marker for peripheral edema before and after esophagectomy in eight patients. Plasma interleukin-6 (IL-6) was also measured by an enzyme-linked immunosorbent assay. Finger edema markedly increased in the immediate postoperative period and remained significantly elevated until after postoperative day (POD) 3 compared to the preoperative value (P < 0.05). Plasma IL-6 also markedly increased in the immediate postoperative period and remained significantly elevated on POD 2 compared to the preoperative value (P < 0.05). The degree of finger edema highly correlated with the level of plasma IL-6 (r = 0.71, P = 0.0001). These findings indicate that peripheral edema after esophagectomy might be caused by a proinflammatory cytokine response.

Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver.

BACKGROUND & AIMS: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H2O2 induces apoptosis in hypoxic rat liver. METHODS: Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H2O2 and stained with the TUNEL method. RESULTS: In the hypoxic liver, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H2O2 induced apoptosis selectively in SECs. CONCLUSIONS: Low-flow hypoxia induces H2O2 production in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the rat liver.

Synthesis and evaluation of N-acetylneuraminic acid-based affinity matrices for the purification of sialic acid-recognizing proteins.

The synthesis of 2-S-(2-aminoethyl) 5-acetamido-3,5-dideoxy-2-thio-D-galacto-2-nonulopyranosidonic acid (1) has been successfully achieved from the precursors methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-S-acetyl-3,5-dideoxy-2-thio-D-glyce ro-alpha-D-galacto-2-nonulopyranosonate (2) and 2-bromo-N-(tert-butoxycarbonyl)-ethylamine (5). Compounds 1 and 2 were coupled, via amino and thioglycosidic linkages, respectively, to epoxy-activated Sepharose 6B. The resultant affinity adsorbents have proved efficient in purifying the sialic acid-recognizing enzyme Vibrio cholerae sialidase, in a one-step process with yields in the order of 60%.

A conformational study of the human and rat encephalitogenic myelin oligodendrocyte glycoprotein peptides 35-55.

Myelin oligodendrocyte glycoprotein (MOG), is considered an important central-nervous system-specific target autoantigen for primary demyelination in autoimmune diseases like multiple sclerosis. We have recently demonstrated that MOG or its derived peptide, MOG-(35-55)-peptide, are able to produce in animals, clinicopathologic signs that mimic multiple sclerosis. The rat MOG sequence spanning amino acids 35-55 [rMOG-(35-55)-peptide] differs from the human sequence [hMOG-(35-55)-peptide] by a single amino acid substitution, i.e. Pro42-->Ser. Mice injected with rMOG-(35-55)-peptide showed severe inflammation and demyelination throughout the central nervous system but, interestingly, mice injected with hMOG-(35 -55)-peptide showed only a few foci of mild inflammation with no demyelination. Circular dichroism and nuclear magnetic resonance spectroscopy have been used to structurally characterise the bioactive peptides hMOG-(35-55)-peptide and rMOG-(35-55)-peptide. In 0.1 M K2HPO4/KOH, 90% H2O/D2O solutions, these derived peptides have been shown, by NMR spectroscopy, to adopt detectable levels of short-range structure in equilibrium with unfolded conformers. On addition of 2,2,2-trifluoro-(2H3)ethanol, rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt folded structures which have nuclear Overhauser enhancements characteristic of a poorly defined alpha-helix over residues 44-51. There are some indications of secondary structure also evident in the N-terminal region of rMOG-(35-55)-peptide. CD spectroscopy has revealed that in aqueous solution both peptides are unfolded but in 2.2.2-trifluoroethanol and, at micellar concentrations of sodium dodecyl sulfate, rMOG-(35-55)-peptide and, to a lesser extent, hMOG-(35-55)-peptide adopt helical conformations. In contrast, at non-micellar concentrations of SDS rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt, according to CD spectroscopy, a beta-structure indicating that the peptides change conformation depending on the microenvironment of the amino acids.

Gene amplification of int-2 and erbB in human esophageal cancer: relationship to clinicopathological variables.

Gene amplification is a relatively frequent event in human malignant tumors and is believed to play an important role in tumor progression. The int-2 and erbB genes are amplified more frequently than any other genes in human esophageal cancer. In order to investigate the correlation between these two proto-oncogenes and the clinical behavior of esophageal cancer, we examined DNA amplification of int-2 and erbB and analyzed their relationship to clinicopathological variables. Genomic DNA was extracted from 21 esophageal squamous carcinomas and normal esophageal mucosa, as well as from 4 metastatic tumors. We used Southern blot analysis for detection of gene amplification. Amplification of int-2 was observed in 13 of 21 cases (62%) and in all the metastatic tumors (4/4; 100%). We found a significant correlation between amplification of int-2 and the length of the primary lesion. Amplification of erbB was detected in 3 of 18 patients (17%). All patients who showed amplification of erbB also demonstrated amplification of int-2. These results suggest that amplification of int-2 or neighboring genes on 11q may participate in tumor progression and metastasis in patients with esophageal squamous cancer.

Direct measurement of doxorubicin concentration in the intact, living single cancer cell during hyperthermia.

BACKGROUND: It is well known that the effect of doxorubicin on cancer cells is enhanced by hyperthermia. The mechanism of this phenomenon is not fully understood. METHODS: Two esophageal squamous cell carcinoma cell lines, TE-2 and TE-6, were used; these cell lines have different sensitivities for doxorubicin. The cells were exposed to 1 microgram/mL of doxorubicin for 30 minutes. With a confocal laser scanning microscope and a transparent warming plate, doxorubicin concentration was measured continuously in the intact, living single cancer cells, and the two-dimensional distribution of the drug during hyperthermia (43 degrees C) was analyzed. RESULTS: A doxorubicin sensitivity difference was confirmed between TE-2 and TE-6 cells by colonogenic assay (P < 0.05). Hyperthermia increased the sensitivity of both cell lines to the drug (P < 0.05) and eliminated the sensitivity difference. Doxorubicin accumulated in the nuclei in both cell lines 30 minutes after exposure to the drug in a time-dependent manner (P < 0.05). Without hyperthermia, the doxorubicin concentration in the nuclei of the TE-2 cells (4.8 +/- 0.3 micrograms/mL) was higher than in the nuclei of the TE-6 cells (2.3 +/- 0.5 micrograms/mL) (P < 0.05). With hyperthermia, there was no significant difference in doxorubicin concentration between the nuclei of the TE-2 cells (20.8 +/- 1.3 micrograms/mL) and the nuclei of the TE-6 cells (16.5 +/- 3.9 micrograms/mL). CONCLUSIONS: Hyperthermia increased the uptake of doxorubicin in the nuclei of cancer cells. Thus, the authors concluded that hyperthermia increases the cells' sensitivity to the drug.

Mediastinal extraadrenal myelolipoma: report of a case.

We herein report a case of surgically resected mediastinal extraadrenal myelolipoma. Myelolipoma is an uncommon tumor composed of adipose tissue and normal hematopoietic elements, and is most often found in the adrenal glands. We could find only five such cases of mediastinal myelolipoma in the English literature.

[Analysis of specificity of resected esophageal cancer patients with a history of apoplexy].

We studied 15 resected cases with a history of apoplexy (2.5%) among 599 cases of esophageal cancer admitted between 1972 and 1993. Fourteen were male, and female, aged 48 to 77 years. Twelve had suffered from cerebral infarction, 2 intracerebral hemorrhage, and one subarachnoid hemorrhage. Duration from apoplexy to operation was between 2 months and 19 years in the cerebral infarction cases, between 8 and 10 years in the intracerebral hemorrhage cases and 4 years in the subarachnoid hemorrhage case. Preoperative neurological disturbance was found in 7 of the 12 cerebral infarction cases, and in both intracerebral hemorrhage cases. Four cases showed hemiplegia, and the other 5 cases showed partial paralysis of limbs. Preoperative complications were found in 7 of the 15 cases, and consisted of diabetes mellitus in 5, hypertension in 4, bronchial asthma in one, and renal dysfunction in one case. Intra- and postoperative complications were found in 11 of the 15 cases, and consisted of anastomotic leakage in 5, delirium in 3, apoplexy in 2, peritonitis in one, ARDS in one, intraoperative cardiac arrest in one, and wound infection in one. Postoperative disorders of consciousness were found in 5 cases, consisting of delirium in 3, and excitation at awakening of anethesia in 2 cases. Rate of direct operative death was 6.7% in preoperative apoplectic patients, and 8.5% in non-apoplectic patients, and there was no significant difference between the 2 groups. On the other hand, rate of postoperative apoplexy was 13.3% in the preoperative apoplectic patients, and 0.4% in non-apoplectic patients. There was a significant difference between them (p < 0.01). But they were cured of it, and left our hospital. It is concluded that active surgical treatment can be indicated for esophageal cancer patients with a history of apoplexy, if more attention is given to the management of diabetes mellitus or hypertension.

Analysis of results of surgery performed over a 20-year period on 500 patients with cancer of the thoracic esophagus.

This study was conducted to examine the long-term outcome of 500 patients who underwent surgery for cancer of the thoracic esophagus during the past 20 years. Favorable results were obtained with postoperative adjuvant radiation and chemotherapy and there were no surgical deaths in the last 5 years. The mortality rate decreased from 17% prior to 1980 to 5% between 1981 and 1993, this being most probably attributable to the decreased incidence of suture leakage. With respect to changes in surgical techniques, during the initial years we performed intrathoracic anastomosis, after which sternal manubrium resection with anterior mediastinal esophagogastrostomy was carried out. Subsequently, we invented a technique for performing esophagogastrostomy via the posterior mediastinum. The posterior mediastinum was selected as the most physiologic route, based on measurement of tissue oxygen tension. Using blood flow determinations obtained by laser-Doppler velocimetry, we concluded that the effectiveness of thicker gastric tubes was superior to that of thin tubes. Esophagogastrostomy was performed in a shallow field in the cervical region, with the anastomosis ultimately positioned in the superior mediastinum and covered with mediastinal pleura.

[A case of primary pulmonary hemangiopericytoma recurred locally 10 years after the first surgery].

Hemangiopericytoma is a rare tumor of vascular origin. This tumor has a malignant potential and often recurs or metastasize. A case of primary pulmonary hemangiopericytoma which recurred locally 10 years after the first surgery is presented. The histological appearance of the tumor had some findings of malignant potential in both of the primary and recurrent lesions. We discussed on malignant potential of this tumor in the number of mitotic figures, cellular atipia, and DNA ploidy pattern.

[Analysis of tracheostomy for patients after thoracic esophageal cancer resection].

Tracheostomy is an available method for respiratory management, but a consensus has not been reached with regard to the significance of postoperative respiratory management. So, we analyzed postoperative tracheostomy patients of esophageal cancer and clarified its significance. We analyzed 26 patients from among 85 who underwent resection for thoracic esophageal cancer between April 1989 and December 1992. We divided them into 3 groups according to the indications of tracheostomy, group I: cases with postoperative pulmonary complications (n: 17), group II: cases of prophylaxis against pulmonary complications (n: 5) and group III: cases with dyspnea deriving from postoperative recurrent nerve palsy (n: 4). Tracheostomy was most often performed between 3 and 4 POD in group I, up to 1 POD in group II and from 5 POD to 7 POD in group III. Long-term respiratory support was needed in 13 cases in group I and 2 cases in group II. The rate of tracheostomy was higher in the case who had postoperative recurrent nerve palsy and received preoperative chemoradiotherapy. All cases excluding a case of MOF had a good clinical course after tracheostomy. We were able to clarify the significance of tracheostomy by dividing tracheostomy patients into 3 groups according to the indications for the procedure. It was concluded that tracheostomy is a very useful technique in the respiratory management of resected thoracic esophageal cancer patients.

[Retrospective study of sputum culture after esophagectomy].

We retrospectively investigated the sputum cultures of patients who underwent esophagectomy (n = 104) from just after operation to 11 postoperative days and evaluated the factors which influenced the cultures. We divided the 0-11 postoperative days into three periods (0-3 postoperative days (p.o.d.), 4-7 p.o.d., 8-11 p.o.d.). The sputum cultures were positive at a rate of 56.7% to 65.4% of patients during the period of observation (0-11 p.o.d.). Gram-negative bacillus was mostly detected. MRSA increased time-dependently. Diabetes mellitus, preoperative irradiation recurrent nerve palsy did not influence the positive rate of the sputum cultures. The positive rate of gram-negative bacillus and gram gram-positive coccus in the sputum of the patients who were given sefem-first generation antibiotics was lower than of patients who were given sefem-second generation antibiotics at 8-11 p.o.d. (p < 0.05). The positive rate of gram-negative bacillus in the sputum of patients who underwent esophagectomy with laryngectomy for cervical esophageal cancer was lower than that of patients who underwent esophagectomy without laryngectomy for thoracic or abdominal esophageal cancer at 4-7 p.o.d. (p < 0.05). The positive rate of gram-negative bacillus in the sputum of patients who underwent intraoperative tracheostomy was lower than that of patients who did not undergo intraoperative tracheostomy at 4-11 p.o.d. No patients had pneumonia during the period of observation except for the secondary lung complications. In conclusion, although we have done a good job of management, we should select the appropriate antibiotics with the patient's background in mind.

[Resection of the posterior mediastinal gastric tube used in reconstruction after radical surgery for esophageal cancer--case reports].

Two patients are presented who underwent resection of a gastric tube placed in the posterior mediastinum during reconstruction following radical esophageal resection for esophageal cancer. The indications for gastric tube resection were bleeding from a peptic ulcer in one and gastric cancer in the other. Case 1: A 72-year-old man, who had undergone a thoracic esophagectomy 3.5 years prior to admission, presented with a chief complaint of hematemesis. The gastric tube was resected and replaced with an antethoracic, pedicled segment of left colon. Pathologic examination of the resected gastric tube revealed a penetrating peptic ulcer. Case 2: A 65-year-old man with esophageal cancer and early gastric cancer underwent thoracic esophagectomy with combined resection of the fundus and lesser curvature of the stomach. One year later, he was found to have a new early gastric cancer in the antrum. The distal portion of the gastric tube was resected and replaced with a pedicled jejunal graft. Of the 526 patients with esophageal cancer treated in our department from 1972 to 1993, peptic ulcers were evident in the gastric tube used to reconstruct the esophagus in only seven cases. The stomach was resected in only one of these patients. Similar patients requiring gastric tube resection have been reported. All six of these cases are reviewed. Cancer of the gastric tube developed in 3 of the 526 patients. Although 74 cases of gastric tube cancer have been reported in the Japanese literature, the patient presented here (case 2) is the first to undergo successful resection of the stomach from the posterior mediastinal position.