African swine fever: A review of cleaning and disinfection procedures in commercial pig holdings.

African swine fever (ASF) is one of the most important diseases in pigs. Since there are no effective vaccines against the virus, farm biosecurity and good farming practices are the only effective tools to prevent the spread of the ASF virus (ASFV) in pig holdings. Hence, an important component of farm biosecurity is the Cleaning and Disinfection (C&D) procedure. Precise indications regarding the ideal disinfectant against ASFV are lacking, but every country has approved and/or authorized a list of biocides effective against ASFV. Lipidic solvents, which destroy the envelope of the virus and commercial disinfectants based on iodine and phenolic compounds are effective in inactivating the ASFV. This review describes the C&D protocol to apply in pig holdings with particular reference to ASFV.

[Translational research and Cancer Plan]. / Recherche translationnelle et plan Cancer.

The French Cancer Plan 2003-2007 has made translational research central to its research programme, to ensure the care-research continuum and the quickest application possible for the most recent discoveries, for the patients' benefit. This is a new field of research, still little-known or ill-understood. A working group, composed of physicians and researchers from academic research and industrial research, sought to define translational research in cancerology and define the issues at stake in it. Translational research needs to develop in close connection with the patients in order to enable a bi-directional flow of knowledge from cognitive research toward medical applications and from observations made on patients toward cognitive research. Placed under the aegis of the French National Cancer Institute and Leem Research, the group has put forth a strategy for implementing translational research in cancerology in France to make it attractive, competitive and efficient and to foster the development of public-private partnerships.

[Macro-economic calculation of spending versus micro-economic follow-up of costs of breast cancer]. / Reconstitution macro-économique des dépenses, suivi micro-économique des coûts du cancer du sein.

BACKGROUND: In the healthcare field, the ability to make economic forecasts requires knowledge of the costs of caring for major diseases. In the case of a semi-chronic condition like cancer, this cost covers all the episodes of care associated with a patient. An evaluation of a macro-economic method of calculating costs for treating non-metastatic cancer, covering all hospital episodes, is proposed. This method is based entirely on the use of annual hospital activity databases, linked to data concerning the incidence of cancer. It allows us to obtain the global cost of care for a neoplasm of a particular site, without the need to reconstruct the whole care pathway of the patients. METHODS: The model was assessed by comparing it's own results, in the particular case of breast cancer to those issuing from a micro-economic follow-up of 115 patients. Data for macro-economic calculation are extracted from the national French hospital database for the year 1999 and from cancer incidence data. The prospective study was done in 1995, in a comprehensive cancer centre. RESULTS: Macro-economic calculation leads to a cost of 14,555 Euro, for primary breast cancer. Prospective follow-up showed a cost of 14,350 Euro (data corrected, 1999 value). With a difference of 1%, there was a clear cohesion of the two results, while a higher level of divergence was noticed (from 1 to 15%) in the comparison between therapeutic techniques. Accuracy and reliability of results were evaluated. CONCLUSION: This method may be extended to all types of neoplasms. This method cannot be used instead of follow-up studies, for cost-efficacy or cost-severity analysis, but may be interesting beyond economic forecasts, in the field of payment per pathology.

[A study based on national DRG data to evaluate work load and practice relating to cancer patients in not-for-profit hospitals]. / Un essai d'exploitation de la base PMSI nationale pour évaluer le volume et les modes de prise en charge du cancer en secteur hospitalier non lucratif.

BACKGROUND: In France there is no reliable information describing the organisation of hospital care for patients with cancer. The present study attempts to clarify this issue taking advantage of an information source that has up to now been unused, namely the national PMSI (Information System Medical program) data base. METHODS: A quantitative study has been carried out regarding cancer management in France using information filed with the PMSI which compiles data related to hospital admissions in all institutions with more than 100 beds and subject to a defined global budget. The "cancer" component of hospital activity was extracted using a specific algorithm which utilized the diagnostic and intervention codes included in the admission summaries. By using the unit of activity as defined by the ISA (Activity Synthetic Index) and the scale of relative cost according to the GHM (Homogeneous Group of patients) it was possible to analyse the information in terms of a balance sheet. RESULTS: The study provided information regarding the costs and methods of management, including therapeutic strategies, for each type of hospital establishment. It is shown that with one death out of six, cancer covers a quarter of all hospital stays, and one sixth of annual hospital expenses. This accounts for 16.2% of ISA ie approximately 29 billion francs (4.6 billion dollars) for the public and semipublic sectors. Surgery, which accounted for 32% of expenditures, appeared to be the most expensive intervention, ahead of chemotherapy (16.3%) and radiotherapy (9.1%). Each type of hospital organisation (university, cancer centre, district hospital) had their own relative figures. CONCLUSION: Through this study the current situation regarding cancer care in hospital has been documented. It has also demonstrated the value of the PMSI data base as a source of information for large scale quantitative studies of health care economics. However, the PMSI does not yet provide details regarding infrastructure or succession of hospital stay. Ultimately, this analysis does not provide any information on the quality or efficacy of care but does define a typological system for health care organisations which could provide information on distribution of resources.

The role of providers in implementation of the National Kidney Foundation-Dialysis Outcomes Quality Initiative: Fresenius Medical Care North America perspective.

This is a brief review of the history of utilization of quality indicators by a major dialysis provider and how those indicators have been modified in response to the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI). Fresenius Medical Care North America (FMCNA) has monitored adequacy of dialysis, anemia management, and nutrition therapy for a number of years, using a self-directed continuous quality improvement program. FMCNA supports the NKF-DOQI Guidelines and has used the DOQI as it continues to enhance its patient quality care program. Specific goals and action thresholds of that program are delineated.

Synthesis and antiulcer activity of novel 5-(2-ethenyl substituted)-3(2H)-furanones.

In order to investigate new antiulcer agents, spizofurone 1 (AG-629) was fragmented and reassembled to generate 5-phenyl-2,2-dimethyl-3(2H)-furanone (bullatenone, 2). Because of the antiulcer activity of 2,5-phenyl-substituted 2,2-dimethyl-3(2H)-furanones (3-6) were made and shown to have poor activity. Insertion of an ethenyl link between the furanone and phenyl rings gave 5-(2-phenylethenyl)-2,2-dimethyl-3(2H)- furanone (7). This compound had better activity than 2. Compounds 8-41 were synthesized to evaluate the SAR in 5-(2-ethenyl substituted)-3(2H)-furanones. Electron-withdrawing substituents on the aromatic ring (8, 10, 19, and 20) gave 2-3-fold higher activity. Further increases in the activity were found when the phenyl ring was replaced by heterocyclic nuclei. Compounds that contained a thiophene (29), pyridine (24-26), or quinoline ring (32) had the best activity. Replacement of the methyl group on the furanone ring with a phenyl (34) or p-fluorophenyl (40) substituent in the 2-pyridine series gave compounds with activity that ranked with the best obtained in this study. The best compounds from the above SAR studies were evaluated in the ethanol-necrosis model for duration of cytoprotection action. Compounds 19, 24, and 29, which had the best duration of action, were tested with AG-629 in the acidified aspirin and indomethacin-induced lesion models. Only compound 24 had equivalent activity with AG-629 in both models.

Rapid induction of early osteoarthritic-like lesions in the rabbit knee by continuous intra-articular infusion of mammalian collagenase or interleukin-1.

Aminophenyl mercuric acetate (APMA)-activated collagenase (C) (60 U/ml) obtained from in vitro cultures of human skin fibroblasts or recombinant interleukin-1 beta (IL-1 beta) (200 U/ml) was infused continuously for 7 days into the rabbit knee synovial space by means of an implanted Alzet osmotic pump. In stability studies in vitro, activated C or IL-1 incubated for 7 days at 37 degrees C, showed no significant loss of biological activity. Alterations in knee cartilage morphology and proteoglycan (PG) content were determined histologically, and the incidence of cartilage damage calculated. C or IL-1 vehicles infused for 7 days, caused no damage. Incidences of damage for C or IL-1 (n = 8-9), respectively, were as follows: loss PG: 88% and 100%; chondrocyte disorganization and loss, 50% and 78%, fissures and or fraying, 25% and 78%; and convergence of inflammatory cells, 25% and 66%. These results confirm the important role of C and IL-1 in cartilage damage.

Inhibition of interleukin-1 (IL-1) induced neutral proteases from rabbit articular chondrocytes by WY-46,135 and WY-48,989.

The effects of potential anti-osteoarthritic compounds both on the direct inhibition of collagenase and neutral protease activities and on IL-1 induced release of neutral proteases from rabbit articular chondrocytes were investigated. WY-46,135 ((+)-N-[[[(5-chloro-2-benzothiazolyl)thio]phenyl]acetyl]-L- cysteine) directly inhibited collagenase activity (IC50 = 15.4 microM). This inhibition was reversible upon dialysis. WY-46,135 also directly inhibited neutral protease activity (IC50 = 16.8 microM) but did not significantly block bacterial collagenase activity at a concentration of 80 microM. In contrast, WY-48,989 (4-[[2-(7-chloro-2-phenyl-2H-pyrazolo[4,3-c]quinolin-4- yl)ethyl]amino]benzonitrile) did not directly inhibit either collagenase (10 microM) or neutral protease (100 microM) activity. Both WY-48,989 and WY-46,135 inhibited IL-1 stimulated release of neutral proteases (IC50 = 3 microM). The activities of these compounds represents two potential approaches for the treatment of osteoarthritis. WY-46,135 combines direct metalloprotease inhibitory activity with the inhibition of IL-1 stimulated neutral protease release from articular chondrocytes while WY-48,989 selectively inhibits the IL-1 induced release of metalloproteases.

Mucosal protective activity of activated aluminum complex.

The antacid ES Riopan was acidified ex vivo to pH 2.5 to completely eliminate its buffering capacity and was then tested as a mucosal protective agent. The pH 2.5 acidified antacid solution was named activated aluminum complex. Activated aluminum complex was 8.2 times more potent than its parent antacid in protecting against acidified aspirin-induced gastric lesions in the rat. Activated aluminum complex had a duration of action greater than 10 h in the ethanol-induced gastric lesion model, while ES Riopan was active for 6 h. Activated aluminum complex was able to inhibit both acid- and nonacid-mediated ulcers in the stomach and intestine. Its mucosal protective activity was not blocked by pretreatment with indomethacin. These results demonstrate that the nonbuffering antacid activated aluminum complex exerted a more potent and longer-lasting mucosal protective activity than its parent antacid. The activity was probably due to the presence of a hexaaquoaluminum cation and supports the argument that antacids possess mucosal protective effects independent of their acid-neutralizing capacity.

N-phenyl-2-pyridinecarbothioamides as gastric mucosal protectants.

A series of substituted 2-pyridinecarbothioamides was synthesized and evaluated for gastric mucosal protectant activity in the rat. Out of this investigation N-(3,5-difluorophenyl)-2- pyridinecarbothioamide (23, AY-31,574) was identified. This compound was much more potent than sucralfate and ranitidine against ethanol-induced lesions. Compound 23 was equipotent with ranitidine against gastric injury caused by stress. Unlike ranitidine, 23 was found to be devoid of antisecretory activity in the pylorus-ligated rat model, making it a selective mucosal protectant. Such a potent selective mucosal protectant may provide a novel clinical approach in treating ulcers.

Cytoprotective and antiulcer activities of the antacid magaldrate in the rat.

The cytoprotective and antiulcer activities of the antacid magaldrate (ES Riopan) as well as its effects on gastric mucosal blood flow and mucus secretions, were determined in the rat. Magaldrate afforded protection against gastric necrotic lesions induced by absolute ethanol (ED50, as magaldrate, 419 mg/kg); gastric ulcers induced by acidified acetylsalicylic acid (ED50 540 mg/kg), stress (cold restraint, ED50 388 mg/kg), indometacin (ED50 281 mg/kg), and pylorus ligation; and intestinal ulcers induced by cysteamine (ED50 243 mg/kg) and indometacin (ED50 184 mg/kg). At a dose of 8 ml/kg (1728 mg/kg magaldrate), the cytoprotective effect of magaldrate against ethanol was evident 1 min after oral administration and lasted more than 8 h. The cytoprotection induced by magaldrate was decreased by pretreatments with the depletor of endogenous thiols, n-ethylmaleimide, or with the cyclooxygenase inhibitor, indometacin. Magaldrate did not affect gastric mucosal blood flow, but it increased gastric mucus secretion. This later effect may be a factor responsible for the cytoprotective activity of the agent. The efficacy of magaldrate may be due not only to its antacid, bile sequestering, and antipeptic activities, but also to its cytoprotective activity. The present results suggest that magaldrate could be effective in preventing gastric damage caused by alcohol and antiinflammatory drugs.

Gastric antisecretory and antiulcer/cytoprotective effects of 2-cyano-3-(ethylthio-3-methylthio)-2-propenoic acid methyl ester.

AY-28,200 (2-cyano-3-(ethylthio-3-methylthio)-2-propenoic acid methyl ester), a new gastric antisecretory/antiulcer agent, inhibited basal and pentagastrin-stimulated gastric acid secretion in the conscious rat (ED50 = 7.6 and 1.9 mg/kg i.g., respectively). For inhibition of basal secretion, peak activity was attained in 5 to 6 h after dosing and was maintained for more than 10 h, with no gastric antisecretory activity occurring at 24 h. The K+ stimulated H+-K+ ATPase activity from rabbit gastric microsomes was inhibited by AY-28,200 (IC50 = 22 mumol/l). AY-28,200 inhibited ethanol-induced gastric lesions, at 3 mg/kg p.o. AY-28,200's cytoprotective effects against ethanol lasted for more than 4 h. AY-28,200 blocked acetylsalicylic acid and stress-induced gastric ulcers but was inactive against indomethacin-induced gastric ulcers. These results suggest that AY-28,200 is a parietal cell proton pump inhibitor with cytoprotective properties, and may produce its cytoprotective effect by stimulating the formation of endogenous prostaglandins.

Activated aluminum complex derived from solubilized antacids exhibits enhanced cytoprotective activity in the rat.

Removing the buffering capacity of aluminum-containing antacids by acidification greatly increased their cytoprotective activity over the parent antacid. Commercially available antacids were acidified with 6 N HCl. Peak mucosal protective activity occurred at pH 2.5, and declined at lower pH. At pH 2.5, the antacid suspensions became solubilized and no acid-neutralizing capacity remained. This solution was named activated aluminum complex. Based on aluminum ion content, each aluminum-containing antacid suspension tested demonstrated a comparable increase in potency on acidification against ethanol-induced lesions. HCl (pH 2.5) was inactive against ethanol-induced lesions. At cytoprotective doses, activated aluminum complex did not cause gastric lesions when orally administered by itself, demonstrating that it is not acting as a local mucosal irritant. The data suggest that solubilization of aluminum-containing antacids in acidic medium enhances their mucosal protective activity, probably by releasing an activated species of aluminum ion reported to be a hexaaquoaluminum cation.

Antisecretory and antiulcer activities of a potent new histamine H2-receptor antagonist with an intermediate duration of action.

The antisecretory activities of 4-(dimethylamino)- N-[2-[3-[3-(1-piperidinyl)methyl]phenoxy]propyl]amino]- 1,2,5-thiadiazol-4-yl]amino]ethyl]-butanamide, S-oxide (AY-29,315) and ranitidine were determined in the rat, dog and monkey. In conscious, chronically cannulated rats, AY-29,315 was 10 and 208 times more potent than ranitidine as an inhibitor of spontaneous gastric acid secretion by the p.o. and i.v. routes, respectively. Tolerance did not develop in the conscious rat with either compound when administered for 8 consecutive days at doses equivalent to 4 times their antisecretory ED50. In lumen-perfused, anesthetized rats, AY-29,315 i.v. was 44 times more potent than ranitidine as an inhibitor of dimaprit-induced acid secretion. In the gastric fistula dog, AY-29,315 was 7.5 times more potent than ranitidine as an inhibitor of dimaprit-induced secretion by the i.v. route but 3 times less potent by the oral route. In the monkey, against dimaprit, AY-29,315 was 3 and 12 times more potent than ranitidine by the oral and i.v. routes, respectively. p.o./i.v. ratios indicate that, relative to ranitidine, the bioavailability of AY-29,315 by the oral route was low, particularly in the dog. In the dog, at 4 times the oral ED50 dose, the antisecretory effect of ranitidine lasted 190 +/- 3 min, while that of AY-29,315 lasted more than 9 h. AY-29,315 was 8 times more potent than ranitidine as an inhibitor of acetylsalicylic acid-induced ulcers in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia.

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.

In vitro enhancement of peripheral blood mononuclear cell natural killer activity following short term incubation with fetal calf serum.

This study demonstrates that short term incubation of blood mononuclear cells (MC) in heterologous sera enhances their natural killer (NK) but not their antibody dependent killer (K) activity, and confirms that NK stimulation is not related to blastogenesis. MC were obtained from healthy donors and incubated with RPMI 1640 supplemented with various serum sources. NK and K activity of incubated vs. fresh MC against SK-N-SH, Chang or Raji cell line targets were compared in a 4-hr 51Cr release assay. A significant (p less 0.01) increase in NK cytotoxicity was detected when MC were incubated with fetal calf serum (FCS) or human AB serum (ABS) at 37 degrees C. When a more sensitive NK target cell (K-562) was used only the cells incubated in FCS demonstrated increased NK cytotoxicity. Augmentation of NK cell activity by FCS was not related to blastogenesis, mitosis, natural antibodies against lymphocytes or target cells, immunoglobulin complexes or alterations in MC OKT4 and OKT8 subpopulations. In contrast to NK activity, K cytotoxicity was not increased after incubation at 37 degrees C in FCS or ABS, and it was depressed in IPT (p less than 0.05). Thus FCS is capable of stimulating NK cell activity against human tumor cell lines in less in less than 24 hr.

A simple non-radioactive method for the simultaneous quantitative determination of stomach empyting and intestinal propulsion in the intact conscious rat.

A simple non-radioactive method for the simultaneous assessment of stomach emptying and intestinal propulsion in intact fasted conscious rats was developed employing Amberlite pellets. The Amberlite pellets were administered by gastric gavage and the rats were killed 20 or 120 min later. The number and percent of the pellets in the stomach and intestines and the distance travelled by each pellet in the small intestine were determined. The distance travelled by the leading pellet in the small intestine was employed as a parameter to determine effects on intestinal propulsion independent of the stomach emptying activity. Chlorisondamine (s.c.), atropine (s.c.), pentobarbital (i.p.) and sesame seed oil (p.o.) inhibited both stomach emptying and intestinal propulsion in a dose-related manner. All these agents also caused a dose-related displacement of the pellets in the small intestine which resulted in a more cephalad-oriented distribution of the pellets. Propantheline (s.c.) exerted a dose-related inhibition on the stomach emptying but not on intestinal propulsion. Carbachol (s.c.) increased both the rate of stomach emptying and that of propulsion in the small intestine.