Prevalence of nodal metastases in the individual lymph node stations for different T-stages in gastric cancer: a systematic review.

BACKGROUND: Gastrectomy with lymph node dissection is the cornerstone of curative treatment of gastric cancer. Extent of lymphadenectomy may differ depending on T-stage, as the rate of lymph node metastases may differ. The objective of this systematic review is to investigate and compare the prevalence of nodal metastases in the individual lymph node stations between different T-stages. METHODS: Data reporting and structure of this systematic review follows the PRISMA checklist. The Medline and PubMed databases were systematically searched. The search included the following Mesh terms: "Stomach Neoplasms", "Lymphatic Metastasis" and "Lymph Node Excision". The primary outcome was the highest prevalence of nodal metastases per T-stage. RESULTS: The initial search resulted in 175 eligible articles. Five articles met the inclusion criteria and were accordingly analyzed. Concerning the lymph node stations 1 to 7, the lymph nodes along the lesser gastric curvature (station 3) show the highest metastases rate (T1: 5.5%, T2: 21.9%, T3: 41.9%, T4: 71.0%). Concerning the lymph node stations 8 to 20, the lymph nodes around the common hepatic artery (station 8) show the highest metastases rate (T1: 0.8%, T2: 7.9%, T3: 14.0%, T4: 28.2%). CONCLUSION: An overall low prevalence of nodal metastases in the individual lymph node stations in early, T1 gastric carcinomas and an overall high prevalence in more advanced, T3 and T4 gastric carcinomas endorse a more tailored approach based on the different gastric T-stages. In addition, a less extensive lymphadenectomy seems justified in early T1 carcinoma. SYNOPSIS: This systematic review provides an overview of the prevalence of nodal metastases for the individual lymph node stations between different T-stages, showing an overall low prevalence in early, T1 gastric carcinomas and an overall high prevalence in the more advanced, T3 and T4 gastric carcinomas.

T-cell factor-4 and MHC upregulation in pigs receiving a live attenuated classical swine fever virus (CSFV) vaccine strain with interferon-gamma adjuvant.

The effect of co-administration of interferon (IFN)-γ in pigs undergoing vaccination with an attenuated strain (LPC) of classical swine fever virus (CSFV) was investigated. Unvaccinated pigs demonstrated pyrexia and died 7-9 days after challenge with virulent CSFV. Pigs receiving the attenuated vaccine remained healthy after virus challenge, except for mild, transient pyrexia, whereas pigs receiving IFN-γ simultaneously with the vaccine demonstrated normal body temperatures after virus challenge. Examination by nested RT-PCR revealed greater viral load in the spleens of the pigs vaccinated with the attenuated CSFV, compared with those that had additionally received IFN-γ. Expression of major histocompatibility complex (MHC) class I and MHC class II molecules was upregulated in the spleens of the IFN-γ treated vaccinated pigs, demonstrated by immunohistochemistry. Based on Western blot analysis, anti-CSFV IgG2 antibodies were elevated in vaccinated pigs by co-administration of IFN-γ (IFN-γ(Hi): P < 0.01; IFN-γ(Lo): P <0.05). By employing the suppression subtractive hybridization technique, RT-PCR, in situ hybridization, and immunohistochemistry, T-cell factor-4 (Tcf-4) mRNA and protein expression were found to be upregulated in the spleens of vaccinated pigs that had received IFN-γ. This study suggests involvement of Tcf-4 in IFN-γ-mediated immune regulation following CSFV vaccination.

Randomised comparison of three tools for improving compliance with occlusion therapy: an educational cartoon story, a reward calendar, and an information leaflet for parents.

BACKGROUND: We previously demonstrated that compliance with occlusion therapy for amblyopia was improved by the use of an educational programme, especially in children of parents of foreign origin and who spoke Dutch poorly. The programme consisted of: (i) a cartoon story for amblyopic children that explained without words why they should patch, (ii) a calendar with reward stickers, and (iii) an information leaflet for parents. In the current study, we assessed the individual effect of each component on compliance. METHODS: We recruited 120 3- to 6-year-old children who lived in a low socio-economic status (SES) area in The Hague and were starting occlusion therapy for the first time. They were randomised to receive one of the components (three intervention groups), or a picture to colour (control group). The randomisation was blinded for treating orthoptist and researcher. Compliance was measured electronically using the Occlusion Dose Monitor (ODM). Primary outcome was percentage of compliance (actual/prescribed occlusion time). Secondary outcome was absolute occlusion hours per day. Parental fluency in Dutch was rated on a five-point scale. RESULTS: Compliance could be measured electronically in 88 of the 120 children; in 32 others, it failed for various reasons. Parental fluency in Dutch was moderate or worse in 36.4 % (p = 0.327). Average compliance was 55 % standard deviation (SD) 40 (n = 18) in the control group, 89 % SD 25 in the group receiving the educational cartoon (n = 25, P = 0.002 compared with control group), 67 % SD 33 (n = 24, P = 0.301) in the reward-calendar group and 73 % SD 40 (n = 21, P = 0.119) in the parent-information-leaflet group. On average, children in the control group occluded 1:46 SD1:19 hours/day, 2:33 SD 1:18 hours/day in the group receiving the educational cartoon, 1:59 SD 1:13 hours/day in the reward-calendar group and 2:18 SD 1:13 hours/day in the parent-information-leaflet group. No child who received the cartoon story occluded less than 1 hour per day, against seven in the reward-calendar group, five in the parent-information-leaflet group and five in the control group. CONCLUSIONS: Although all three components of the programme improved compliance with occlusion therapy in children in low-SES areas, the educational cartoon had the strongest effect, as it explained without words to a 4- to 5-year-old child why it should wear the eye patch.

[Toxic plasma concentration of clozapine in inflammatory processes]. / Toxische plasmaconcentratie van clozapine bij ontstekingsprocessen.

Clozapine has a narrow therapeutic range. The threshold value for plasma concentrations is 350 µg/l. If plasma concentrations exceed that value, serious side-effects can occur. An increase in plasma concentrations can occur as a result of inflammatory processes which may or may not be caused by an infection. Two cases are discussed in which the plasma concentration of clozapine increased as a result of an inflammatory reaction and signs of intoxication were observed. These developments seemed to be due to cholecystitis and bacterial pneumonia respectively. The clinical presentation and pathophysiology are discussed in relation to inflammatory processes.

[Antipsychotic agents and stimulants: a judicious combination?]. / Antipsychotica en stimulantia: een zinvolle combinatie?

A 31-year-old male, diagnosed with schizophrenia and receiving maintenance treatment with olanzapine, was prescribed methylphenidate for comorbid attention deficit hyperactivity disorder (adhd). The adhd symptoms diminished and there were hardly any side-effects. No increase in psychotic symptoms occurred. The patient used far fewer amphetamines and benzodiazepines. In theory, stimulants and antipsychotics produce opposite effects. Relevant literature on the subject is discussed.

Pathology and viral distributions of the porcinophilic foot-and-mouth disease virus strain (O/Taiwan/97) in experimentally infected pigs.

Twenty-four specific pathogen free pigs were inoculated intradermally at the front-right heel bulb with 0.5 ml of viral suspension containing 10(6.0)tissue culture infectious dose (TCID(50)) with the porcinophillic strain (O/Taiwan/97) of foot-and-mouth disease virus (FMDV) isolated from the epizootic of FMD in Taiwan in 1997. Two pigs were euthanatized at 8 h, 1, 2, 3, 6, 8, 12, 15, 21, 26 and 63 days post-inoculation (DPI), and two pigs remained for long-term observation and terminated at 400 DPI. Typical symptoms of depression and inappetence appeared in the inoculated pigs at 1 DPI and subsided by 7 DPI. Vesicles developed in the epidermis over non-inoculated metacarpals joints at 1 DPI and vesicles in the mouth and on the snout were noticed at 2 DPI. Lesions in the feet were characterized by necrosis in the stratum spinosum, intercellular oedema, and vesicle formation accompanied by neutrophilic and mononuclear cells infiltration. Baby hamster kidney-21 cell cultures were used for virus isolation and viraemia was detected beginning at 1 DPI and persisted till 3 DPI and was no longer detectable when neutralizing antibody (NA) developed at 4 DPI. However, virus was isolated from skin samples from 1 to 12 DPI, from faeces from 2 to 8 DPI, and from 95% oesophageal-pharyngeal (OP) fluid samples at 8 HPI. Among the samples tested in this study, skin vesicles had the highest virus titre, 10(8.63) TCID(50). No virus was isolated from the skin or visceral organs obtained from post-mortem at day 15 after infection and the virus was not detectable from the OP fluid from 12 DPI till the end of this study (400 DPI). By using reverse transcriptase-polymerase chain reaction, viral RNA was detected first from the tissues at the inoculation site at 1 DPI, and still detectable at 21 DPI. Neutralizing antibody emerged at 4 DPI and the geometric mean NA titre reached to 1:861 and 1:1097 at 21 and 301 DPI respectively. The re-growth of hoof began at 21 DPI; however, minimal lesions including remnants of the old hoof were still presented at the end of this study. These results suggest that monitoring pig's hooves for residual lesions should be part of the FMD diagnosis.

Immune responses to foot-and-mouth disease virus in pig farms after the 1997 outbreak in Taiwan.

This paper reports on a retrospective study of the antibody responses to structural and non-structural proteins of FMD virus O Taiwan 97 in six pig herds in Taiwan in the year after the 1997 Taiwanese FMD outbreak. All herds were vaccinated against FMD after the outbreak as part of the countrywide control program. Three of the herds had confirmed FMD infections (herds N, O and P) and three herds remained non-infected (herds K, L and M). The serum neutralizing antibody titers and the non-structural protein ELISA (NSP) antibody responses in sows and 1-month-old pigs in the infected herds were higher than in the non-infected herds, but over time a number of positive NSP reactors were detected. From the serological studies and the herd monitoring and investigations it was considered that the FMD NSP positive reactors may not have constituted a true reservoir of FMD virus infection especially in herds where susceptible pigs were no longer present post-exposure or post-vaccination. Pigs vaccinated with an unpurified FMD type O vaccines being used at that time also showed false positive responses for NSP antibodies.

Immune responses of pigs to commercialized emulsion FMD vaccines and live virus challenge.

The immune response to structural and non-structural proteins (NSPs) was studied on sequential serum samples in swine from O/Taiwan/97 FMDV challenge studies, outbreaks and after vaccination. The results showed that pigs vaccinated with a commercial vaccine prior to or after infection maintained high neutralizing antibody titers with gradual decline from peak titers over the duration of this study. However, neutralizing antibody titers in non-vaccinated pigs only reached moderate levels 2-4 weeks post infection and remained low thereafter. For the 3B and 3ABC NSP antibody ELISA responses, there were gradually decreasing levels of NSP antibody over time. In multiple vaccinations, all pigs showed significant increases in neutralizing antibodies after booster vaccination. For the 3B NSP antibody ELISA after vaccination, the mean S/P ratios for pigs vaccinated with all three FMD vaccines were all below the 0.23 cut-off value set by the manufacture, but some sera from individual vaccinated pigs gave results above this cut-off after primary or secondary vaccination. However, with the 3ABC NSP antibody ELISA, all sera from vaccinated pigs had negative results for NSP antibody for all time points.

Comparison of sensitivity and specificity in three commercial foot-and-mouth disease virus non-structural protein ELISA kits with swine sera in Taiwan.

Three commercialized ELISA kits for the detection of antibodies to the non-structural proteins (NSPs) of FMD virus were compared, using sera from uninfected, vaccinated, challenged and naturally infected pigs. The kinetics of the antibody response to NSPs was compared on sequential serum samples in swine from challenge studies and outbreaks. The results showed that ELISA A (UBI) and ELISA B (CEDI) had better sensitivity than that of the 3ABC recombinant protein-based ELISA C (Chekit). The peak for detection of antibodies to NSPs in ELISA C was significantly delayed in sera from natural infection and challenged swine as compared to the ELISA A and B. The sensitivity of the three ELISAs gradually declined during the 6-month post-infection as antibodies to NSP decline. ELISA kits A and B detected NSP antibody in 50% of challenged pigs by the 9-10th-day and 7-8th-day post-challenge, respectively. ELISA B and C had better specificity than ELISA A on sequential serum samples obtained from swine immunized with a type O FMD vaccine commercially available in Taiwan. Antibody to NSPs before vaccination was not detected in swine not exposed to FMD virus, however, antibody to NSPs was found in sera of some pigs after vaccination. All assays had significantly lower specificity when testing sera from repeatedly vaccinated sows and finishers in 1997 that were tested after the 1997 FMD outbreak. However, when testing sera from repeatedly vaccinated sows or finishers in 2003-2004, the specificity for ELISAs A, B and C were significantly better than those in 1997. This effect was less marked for ELISA A. The ELISA B was the best test in terms of the highest sensitivity and specificity and the lowest reactivity with residual NSP in vaccinates.

Phylogenetic analysis of classical swine fever virus in Taiwan.

Two envelope glycoprotein (Erns and E2) regions of the classical swine fever virus (CSFV) were amplified by RT-PCR and sequenced directly from 158 specimens collected between 1989 and 2003 in Taiwan. Phylogenetic analysis of the two regions revealed a similar tree topology and the Erns region provided better discrimination than the E2 region. One hundred and fifteen isolates out of the 158 isolates were clustered within subgroup 2.1 (further classified as 2.1a and 2.1b) and 2.2, which were considered to be likely of the introduced strains, whereas the remaining 43 isolates were clustered within subgroup 3.4 and were considered to be of the endemic strains. The subgroup 2.1a viruses were first detected in 1994 and predominated from 1995 onwards. However, subgroup 3.4 viruses were prevalent in the early years, not being isolated after 1996. We have observed a dramatic switch in genotype from subgroup 3.4 to 2.1a. The subgroup 2.1a isolates are closely related to the Paderborn and Lao isolates, whereas 2.1b isolates have a close relationship to the Chinese Guangxi isolates. The phylogenetic tree of 27 CSFV sequences based on the complete envelope glycoprotein gene (Erns-E2) displayed better resolution than that based on the complete open reading frame.

Efficacy of foot-and-mouth disease vaccine in pigs with single dose immunization.

Two experiments were conducted to demonstrate the efficacy of a commercial foot-and-mouth disease (FMD) vaccine in pigs born to well-vaccinated sows at various ages with a single injection under field conditions. The first experiment showed that single dose vaccination of pigs could be conducted at an age younger than 10 weeks. Second experiment demonstrated that pigs vaccinated once at the age of 8 weeks had mean serum neutralization (SN) titer of 1.89+/-0.95 log(10)SN(50) with full protection by challenge test at the age of 24 weeks. Results indicate that the most appropriate age for single dose FMD vaccination in pigs born to well-vaccinated sows would be at 8 weeks.

Optimization of foot-and-mouth disease vaccination protocols by surveillance of neutralization antibodies.

An appropriate immunization program for pigs in a foot-and-mouth disease (FMD) endemic area was proposed based on data analysis obtained from serological surveillance in Taiwan, after an intensive vaccination program. To provide an adequate passive immunity for piglets, gilts that have completed two basic vaccinations must be boosted once before breeding. To achieve an efficient response to the FMD vaccine for piglets born to well vaccinated sows, vaccination need to be delayed until 10-12 weeks of ages for the first immunization, followed by a boost 4 weeks later.

The effect of brief neonatal exposure to cows' milk on atopic symptoms up to age 5.

AIMS: To determine the effect of brief early exposure to cows' milk on the expression of atopy during the first five years of life. METHODS: Follow up analysis of a double blind, placebo controlled, randomised feeding intervention trial (BOKAAL study). Subjects were 1108 children from 1533 initially randomised breast fed neonates in the Netherlands. Atopic disease and prevalence of allergic symptoms at age 1, 2, and 5, and specific IgE at age 1 and 5 were determined. RESULTS: Atopic disease in the first year was found in 10.0% (cows' milk) versus 9.3% (placebo) of the children, with a relative risk (RR) of 1.07. No differences were found in the second year either. At age 5, atopic disease was found in 26.3% (cows' milk) versus 25.0% (placebo), RR 1.05. There was no difference in the prevalence of allergic symptoms. Specific IgE to cows' milk (RAST positive 2+ or more) was 5.8% (cows' milk) versus 4.1% (placebo) at age 1 (RR 1.43), and 5.3% versus 3.0% at age 5 (RR 1.77). There was no difference in sensitisation to other common allergens between the two groups. CONCLUSION: Early, brief exposure to cows' milk in breast fed children is not associated with atopic disease or allergic symptoms up to age 5.

Molecular characterization of foot-and-mouth disease virus isolated from ruminants in Taiwan in 1999-2000.

In 1999, 10 sporadic outbreaks of cattle foot-and-mouth disease (FMD) occurred in Taiwan. By the time, infection was limited to the Chinese yellow cattle (a native species of beef cattle in Mainland China), which did not develop vesicular lesions under field conditions. Five viruses isolates obtained from individual farms were confirmed to be the serotype O FMD virus (O/Taiwan/1999). During January-February 2000, however, this virus has spread to dairy cattle and goat herds, causing severe mortality in goat kids and vesicular lesions in dairy cattle. Partial nucleotide sequence of the capsid coding gene 1D (VP1) was determined for the virus isolates obtained in this study. Phylogenetic analysis of the VP1 sequences indicated that the O/Taiwan/1999 viruses shared 95-97% similarities to the virus strains isolated from the Middle East and India. The species susceptibility of the O/Taiwan/1999 virus was experimentally studied in several species of susceptible animals, showing that the virus did cause generalized lesions in dairy cattle and pigs, however, it would not cause vesicular lesions on the Chinese yellow cattle and the adult goats. These studies suggested that the O/Taiwan/1999 virus was a novel FMD virus of Taiwan and it presented various levels of susceptibility in cattle species.

Enhancement of the immunity to foot-and-mouth disease virus by DNA priming and protein boosting immunization.

Subunit vaccination is effective in eliciting humoral responses to a variety of viral antigens, however, it has not generated persistent protective immunity to foot-and-mouth disease virus (FMDV). In this study, we observed that priming mice with a DNA plasmid encoding VP1 of the FMDV O/Taiwan/97 capsid protein followed by boosting with a VP1 peptide conjugate (P29-KLH) resulted in production of not only high titers of antibodies but also antibodies with FMDV neutralizing activities. Moreover, the mice immunized in this manner cleared the virus from their sera in FMDV challenge experiments. Mice subjected to DNA plasmid priming and P29-KLH protein boosting had relatively higher ratio of IgG2a/IgG1 than those primed and boosted with P29-KLH conjugate. Addition of an oligodeoxynucleotide (ODN) containing immunostimulatory cytosine-phosphate-guanosine (CpG) motifs to P29-KLH conjugate also induced a higher ratio of IgG2a/IgG1 and significantly higher titer of neutralizing antibodies. These results indicate that treating animals with DNA plasmids priming and FMDV antigen(s) boosting may elicit immunity to FMD and this immune response may be augmented by CpG ODN.

Synthetic peptide-based vaccine and diagnostic system for effective control of FMD.

We have designed synthetic peptides corresponding to two different regions of the genome of foot-and-mouth disease virus (FMDV) that are effective as (a) a vaccine or (b) a diagnostic reagent which differentiates convalescent from vaccinated animals, respectively. The peptide vaccine is based on a sequence from the prominent G-H loop of VP1, one of the four capsid proteins. The sequence was optimized by the inclusion of a cyclic constraint and adjoining sequences, and broader immunogenicity was obtained by the incorporation of consensus residues at hypervariable positions. The peptide also included a promiscuous T-helper epitope for effective immunogenicity in outbred populations of large animals.The diagnostic reagent, a peptide based on non-structural (NS) protein 3B, is used in immuno-assays for the detection of antibodies. Antibodies to this NS protein are present in the sera of infected animals but not in the sera of vaccinated animals. The VP1 peptide can be used in complementary immuno-assays for confirmation of NS test results and to monitor for vaccination. This system for differential diagnosis is important to establish the disease-free status of a country.

Characteristics of foot and mouth disease virus in Taiwan.

Since March 1997 two strains of foot and mouth disease (FMD) virus have found their way into Taiwan, causing severe outbreaks in pigs and in Chinese yellow cattle. Outbreaks occurred in March 1997 were caused by a pig-adapted virus strain (O/Taiwan/97) which did not infect other species of cloven-hoofed animals by natural route. The epidemic spread over the whole region of Taiwan within two months and the aftermath was 6,147 pig farms infected and 3,850,746 pigs destroyed. In June 1999, the second strain of FMD virus (O/Taiwan/99) was isolated from the Chinese yellow cattle in the Kinmen Prefecture and in the western part of Taiwan. By the end of 1999, Chinese yellow cattle were the only species infected and those infected cattle did not develop pathological lesions. Seroconversions of serum neutralization antibody and on non-structural protein (NSP) antibodies were the best indicators for infection in non-vaccinated herds. The infected animals, however, excreted infectious levels of virus to infect new hosts. Based on the detection of the specific antibody to FMD virus, and virus isolation from oesophageal-pharyngeal (OP) fluid samples, ten herds of Chinese yellow cattle located in Kinmen and Taiwan were declared to have been infected. During the period of January to March 2000, however, five outbreaks caused by FMD virus similar to the O/Taiwan/99 virus occurred in four prefectures of Taiwan. The infected species included goats, Chinese yellow cattle and dairy cattle. Those outbreaks have caused high mortality in goat kids under two weeks old and also developed typical clinical signs of infection in dairy cattle.

Molecular epidemiological studies on foot-and-mouth disease type O Taiwan viruses from the 1997 epidemic.

Sequence diversity was assessed of the complete VP1 gene directly amplified from 49 clinical specimens during an explosive foot-and-mouth disease (FMD) outbreak in Taiwan. Type O Taiwan FMD viruses are genetically highly homogenous, as seen by the minute divergence of 0.2-0.9% revealed in 20 variants. The O/HCP-0314/TW/97 and O/TCP-022/TW/97 viral variants dominated FMD outbreaks and were prevalent in most affected pig-raising areas. Comparison of deduced amino acid sequences around the main neutralizable antigenic sites on the VP1 polypeptide showed no significant antigenic variation. However, the O/CHP-158/TW/97 variant had an alternative critical residue at position 43 in antigenic site 3, which may be due to selective pressure in the field. Two vaccine production strains (O1/Manisa/Turkey/69 and O1/Campos/Brazil/71) probably provide partial heterologous protection of swine against O Taiwan viruses. The type O Taiwan variants clustered in sublineage A1 of four main lineages in the phylogenetic tree. The O/Hong Kong/9/94 and O/1685/Moscow/Russia/95 viruses in sublineage A2 are closely related to the O Taiwan variants. The causative agent for the 1997 epidemic presumably originated from a single common source of type O FMD viruses prevalent in neighboring areas.