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.

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.

[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.

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.

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.

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.

The growth of oral bacteria on saliva.

The present experiments were aimed at studying the degradation of salivary glycoproteins by the oral microflora. To this end, S. sanguis I strain Ny476 and S. sanguis II (S. mitior) strain Ny581 were grown continuously in human-whole saliva. Under these conditions, the strains produced a variety of cell-associated hydrolytic activities, including glycosidases, exo- and endopeptidases, and esterases. S. sanguis II generally exhibited higher levels of enzyme activity than did S. sanguis I, in particular of neuraminidase that was produced only by S. sanguis II. In accordance, S. sanguis II had a higher cell yield and consumed a higher proportion of the sugars and sialic acid in the glycoproteins than did S. sanguis I. Interestingly, S. sanguis I, which is devoid of neuraminidase, is known to have a lectin with specificity for sialic acid, whereas S. sanguis II has affinity for galactose residues in the glycoproteins. We propose that specific binding of glycoproteins by oral bacteria constitutes a mechanism to collect nutrients in the vicinity of the cell. The special ability of S. sanguis II to utilize saliva for growth was further exemplified by its selection in batch-wise enrichments of dental plaque on saliva. The microflora in these enrichment cultures always consisted of Peptostreptococcus micros, S. sanguis II, and Fusobacterium nucleatum as the dominant organisms. Further, S. mitis and Gemella haemolysans were generally found to be present. The enrichment cultures produced a wide variety of mainly cell-bound hydrolytic enzymes. This resulted in almost complete breakdown of salivary glycoproteins in the culture.

Effects of highly concentrated stannous fluoride and chlorhexidine regimes on human dental plaque flora.

The aim of this study was to determine the effect of an intensive antimicrobial treatment on the number of Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus/Actinomyces naeslundii, and the total Colony-forming Units (CFU) in plaque. The dentition of human volunteers was treated in a dental office with either chlorhexidine (5%) or stannous fluoride (8%). Following the office treatment with chlorhexidine, selected volunteers rinsed daily at home for seven or 49 days with chlorhexidine solution (0.2%), while another group flossed daily at home for seven days with dental floss impregnated with chlorhexidine. On days one, seven, 21, 35, and 49 after the local applications, we took saliva samples and plaque samples from fissures, smooth surfaces, and approximal areas. Chlorhexidine and stannous fluoride suppressed S. mutans and the Actinomyces species on all surfaces and in saliva. S. mutans on tooth surfaces was suppressed for approximately seven days and returned to the baseline level at day 21. A. viscosus/naeslundii was suppressed for more than seven days on the teeth. S. sanguis and the total CFU returned to the baseline level within seven days on all surfaces and in saliva. Rinsing or flossing with chlorhexidine suppressed S. mutans during the period of time that these supplements were used. Brushing for seven days with chlorhexidine gel (1%) without a preceding intensive chlorhexidine treatment had virtually no effect on S. mutans in approximal areas and in saliva, but suppressed S. mutans in fissures and on smooth surfaces.

Growth of micro-organisms from supragingival dental plaque on saliva agar.

The role of saliva in supporting the growth of dental plaque has scarcely been investigated. We have studied the growth and recovery of micro-organisms from dental plaque samples on saliva-agar plates, prepared from filter-sterilized wax-stimulated whole saliva. Under optimal conditions, the mean recovery of plaque samples on saliva agar was about 50% (range, 22-77) of the recovery on blood agar. Addition of 2.5 mmol/L dithiothreitol (DTT) strongly facilitated filter-sterilization of saliva, but DTT concentrations higher than 1 mmol/L reduced the recovery of plaque micro-organisms on saliva agar. Catalase (100 U/ml) offered protection against the inhibitory effect of DTT. Addition of glucose (1-5 mmol/L) increased only slightly the recovery of plaque micro-organisms on saliva agar. When supragingival plaque was plated on saliva- and blood-agar plates, the composition of the microflora isolated from saliva agar strongly resembled that isolated from blood agar. The predominant species--i.e., Streptococcus and Actinomyces--all grew on saliva agar though usually in numbers somewhat lower than those on blood agar. In addition, most species normally found only in low proportions in supragingival dental plaque were also found to grow on saliva agar. Collectively, the results lead to the conclusion that the supragingival microflora can utilize saliva as a complete source of nutrients.

A conceptual model for the co-existence of Streptococcus spp. and Actinomyces spp. in dental plaque.

One of the most important questions in ecology is how to explain the co-existence of the variety of physiologically related organisms in the same habitat. A model is presented for the co-existence of Streptococcus species and Actinomyces species in dental plaque. The hypothesis is that these organisms co-exist because they simultaneously utilize several carbon and energy substrates. The hypothesis follows from the observation that the growth yield of oral streptococci and actinomyces in saliva is limited by carbohydrate. Preliminary experiments were undertaken to test the hypothesis using mixed chemostat cultures and gnotobiotic rats. Competition between S. mutans K1R and A. viscosus Ut2 in mixed chemostat cultures on glucose and asparagine was hampered by the early appearance of high-glucose-affinity variants of A. viscosus. From the physiological characteristics of S. sanguis and S. milleri, it might be predicted that simultaneous utilization of carbohydrate and arginine would enable these organisms to co-exist with S. mutans in an ecosystem. To test this mechanism under natural conditions, germ-free rats were inoculated with a combination of S. mutans K1R and S. sanguis P4A7 or the combination S. mutans K1R and S. milleri B448. The rats were fed on three different diets: (1) 58% cornstarch; (2) 48% cornstarch and 10% sucrose; and (3) 53% cornstarch and 5% arginine. The results of this experiment demonstrated that dietary arginine caused a significant decrease of the ratios K1R/P4A7 and K1R/B448 in dental plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Colonization of the teeth of rats by human and rodent oral strains of the bacterium Actinomyces viscosus.

The mouths of rats were infected with human and rodent strains of A. viscosus and streptomycin-rifamycin-resistant (SR) mutants of these strains. The establishment, adherence to the teeth and cell dose required for infection were determined. Human and rodent strains established equally well on the teeth and did not differ in their initial adherence to teeth. The cell dose required for infection was much lower for rodent than for human strains (less than 10(5) compared to 10(7) - 10(8) c.f.u.). The SR mutants established as well as their parents except for one SR strain, that did not establish at all. Another SR mutant appeared to have lost its SR resistance after passage through the animal. The results stress the need of in-vivo testing of antibiotic resistant mutants to be used in ecological studies.

The pattern of experimental colonization of a human and a rodent strain of the bacterium Actinomyces viscosus on the dentition of the rat.

Samples were taken from mesial, buccal, lingual and approximal sites and from fissures. Initially, most A. viscosus were recovered from the retention sites. With the exception of lingual sites during the period of exponential growth, the apparent doubling times calculated for A. viscosus Nyl SR remained within narrow limits for all locations. After cessation of exponentional growth, both strains had colonized all surfaces. However, the rodent strain A. viscosus Nyl SR had formed 30-800 times larger populations on the smooth surfaces than the human strain A. viscosus Ut2 . On the retention sites, the populations of both strains were not significantly different.

The natural course of habitual abortion.

In recurrent spontaneous abortion an immunological fetal-maternal imbalance has been postulated and successes of immunotherapy have been described. A prospective study on the reproductive performance of untreated women with three abortions of unknown etiology has not been performed. The benefit of therapy can only be estimated if the natural course of the disease is known. The aim of this study was to investigate prospectively the abortion rate in a well-defined group of women with a history of habitual abortion of unknown etiology and to test the hypothesis that immunologic factors are involved. Fourty-four couples were taken into study. The overall pregnancy rate in the first subsequent pregnancy was 62%. Neither significant increased sharing of Human Leucocyte Antigens (HLA) nor an aberrant mixed lymphocyte reactivity in this group was found when compared to control random matings. The presence or absence of antipaternal antibodies did not correlate with the outcome of the subsequent pregnancy. It is concluded that the prognosis of untreated patients with habitual abortion is favourable and that no aberrant immunologic reactivity could be demonstrated by means of up-to-date diagnostic procedures.

Humoral immunity in normal and complicated pregnancy.

To evaluate the role of some immunological phenomena involved in the pathogenesis of preeclamptic toxaemia, we studied the humoral immune reactivity in patients with preeclamptic toxaemia during the third trimester of pregnancy, and three days and six weeks after delivery. The results were compared with those of patients with intrauterine growth retardation and with uneventful pregnancy. During the third trimester, patients with complicated preeclamptic toxaemia had significantly lower IgG, CH50, C4 and C3 levels than normal pregnants. Post-partum levels of IgM were significantly higher than in all other groups of patients. Circulating immune complexes were not detectable by a C1q binding assay in patients and controls. However, with a conglutinin binding assay and a granulocyte phagocytosis test complexes were demonstrable in patients with complicated preeclampsia (incidence 44% and 33%, respectively). In addition, 66% of these patients showed deposits of immunoglobulins and complement components in superficial blood vessels of the skin biopsy, suggestive of the presence of tissue deposits of immune complexes. This was found in about 30% of the other patient groups and in none of control pregnants. Allo-antibodies to lymphocytes were present in 63% of complicated preeclamptic toxaemia patients and 22% of normal pregnants. Our data show several changes in humoral immune reactivity in preeclamptic toxaemia which may contribute to the pathogenesis of this disorder.

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.