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.

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.

Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study.

BACKGROUND: Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE-mediated allergy in initially nonatopic children. OBJECTIVE: To examine the cross-sectional relation between IgG to foods (i.e. mixture of wheat and rice, mixture of soybean and peanut, egg white, cow's milk, meat, orange and potato) and specific IgE to cat, dog, mite, milk and egg white in 1-year-old children. METHODS: All atopic children (n = 120; 58 with and 62 without eczema) and a random sample of the nonatopic children (n = 144) of the Bokaal study were tested on their IgG response to foods. The IgG results of the food assays were dichotomized high or low using the 66th centile as a cut-off value. RESULTS: Atopic children more often had high IgG levels to foods than nonatopic children. IgG to egg white (OR = 7.50) and mixture of wheat and rice (OR = 4.79) were most strongly associated with positive specific IgE. In a stepwise logistic regression analysis egg white, mixture of wheat and rice, and orange were selected (OR = 3.76, OR = 2.43, and OR = 2.11, respectively). In children without eczema higher levels of IgG to foods were still significantly associated with atopy, which was most prominent for egg white, orange and cow's milk. CONCLUSION: An increased IgG antibody level to foods, especially to egg white, orange, and mixture of wheat and rice, indicates an increased risk of having IgE to cat, dog, mite, egg and/or milk allergens, even in the noneczematous group. Therefore, in another prospective study we are currently investigating the usefulness of IgG in early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing allergic diseases in the future.

Randomised controlled trial of brief neonatal exposure to cows' milk on the development of atopy.

OBJECTIVE: To determine the effect of brief early exposure to cows' milk on atopy in the first 2 years of life. DESIGN: Double blind, placebo controlled, randomised feeding intervention trial (Bokaal study). SETTING: Dutch midwifery practices. PARTICIPANTS: 1533 breast fed neonates. INTERVENTION: Exposure to cows' milk protein (n = 758) or a protein free placebo (n = 775) during the first 3 days of life. MAIN OUTCOME MEASURES: Clinical atopic disease and any positive radioallergosorbent (RAST) tests at 1 year of age. RESULTS: Atopic disease in the first year was found in 10.0% (cows' milk) v 9.3% (placebo) of the children, with a relative risk of 1.07; in the second year, atopic disease was found in 9.6% v 10.2%, respectively, with a relative risk of 0.94. Per protocol analysis showed similar results. Any RAST positive test was found in 9.4% (cows' milk) v 7.9% (placebo) of children, with a relative risk of 1.19. Stratified analysis for high family risk of allergy showed a doubled incidence of atopic disease but no effect from the intervention. CONCLUSION: Early and brief exposure to cows' milk in breast fed children does not increase the risk of atopic disease in the first 2 years.

Early recurrent miscarriage: histology of conception products.

The histopathological appearance of conception products from 44 women with recurrent miscarriage was compared with those obtained from 105 women with sporadic miscarriage. Abnormal villi, suggesting fetal chromosomal abnormalities, were found in 62% of women with a recurrent miscarriage and in 58% of those with sporadic miscarriage. This difference is not statistically significant.

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.

Keratinolytic activity of cutaneous and oral bacteria.

A test was developed to measure the keratinolytic activity of cutaneous and oral bacteria. Keratin, labeled with fluorescein isothiocyanate, was used in a phosphate buffer (pH 7.2) with 1 mM dithiothreitol. The degradation of keratin was estimated by measuring the fluorescence of the degradation products in the supernatant of the reaction mixtures in a luminescence spectrometer. Several oral and cutaneous bacteria were investigated: Bacteroides gingivalis, Bacteroides intermedius, Treponema denticola, Actinomyces odontolyticus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Brevibacterium epidermidis, Brevibacterium lines, Corynebacterium glutamicum, Corynebacterium minutissimum, Corynebacterium ovis, and Rhodococcus equi. The dermatophyte Trichophyton rubrum was used as a control organism. The test offered a simple and quantitative method for the estimation of keratin degradation and enabled us to show keratinolytic activity in Trichophyton rubrum, S. epidermidis, S. haemolyticus, B. linens, B. epidermidis, Bacteroides gingivalis, and Treponema denticola. The keratinolytic activity was cell bound and heat sensitive. The presence of dithiothreitol stimulated the degradation of keratin to mainly high-molecular-weight products.

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.

Enrichment of subgingival microflora on human serum leading to accumulation of Bacteroides species, Peptostreptococci and Fusobacteria.

This study was undertaken to identify ecological factors that favour opportunistic pathogenic species in the subgingival microflora. In a first approach, human serum as a substitute for gingival exudate, was used for batch-wise enrichment of subgingival plaque. The microflora resulting after 5-6 enrichment steps consisted of black-pigmented and non-black-pigmented Bacteroides species, Peptostreptococcus micros and Fusobacterium nucleatum as the main organisms. It is noted that the same group of species was found to be enriched independent upon the origin of the subgingival plaque sample. It was suggested that these organisms are favoured by the increased flow of gingival exudate during inflammation. The consortium of organisms was capable of selective degradation of serum (glyco-)proteins. Four different types of degradation occurred. After a prolonged period of growth complete degradation of immunoglobulins, haptoglobin, transferrin and complement C3c was observed. Partial degradation of immunoglobulins, haptoglobin, transferrin, albumin, alpha 1-antitrypsin and complement C3c and C4 was generally observed after 48 h of growth. Besides, immunoglobulin protease activity yielding Fc and Fab fragments was found. The consortium was also capable of consuming carbohydrate side-chains as indicated by an altered electrophoretic mobility of the serum glycoproteins.

Estimation of growth parameters for some oral bacteria grown in continuous culture under glucose-limiting conditions.

The coexistence of bacteria in natural environments can often be explained in terms of competition for a growth-limiting substrate(s), and the outcome of such competition depends upon relevant growth parameters such as substrate affinity and yield. Dental plaque bacteria are frequently carbon and energy limited. Growth parameters for seven oral Streptococcus species and one Actinomyces viscosus strain were estimated under glucose-limited conditions in continuous culture. In all strains, mixed-acid fermentation occurred at low growth rates, while amounts of lactate increased at higher growth rates. Two important growth parameters, mumax and Y glucose, were very similar in the two serotype c Streptococcus mutans strains (T8 and Ingbritt), one of the serotype d/g Streptococcus mutans strains (OMZ65), and the two Streptococcus milleri strains (699B3 and B448). Two other serotype d/g S. mutans strains (KIR and B13) were divergent from this group and had lower mumax values and a lower Y glucose. The maintenance energy coefficients were lower in the S. mutans serotype c strains, and the highest values were observed in the S. milleri strains. While A. viscosus had a lower mumax, its lower maintenance rate and significantly higher yield indicate that it deals much more efficiently with glucose than do the streptococci. The most striking feature of amino acid utilization was that arginine was completely consumed by S. milleri strains; similarly, A. viscosus used up all available asparagine as did one of the S. milleri strains at faster growth rates. It is suggested that the ability of strains of S. milleri and S. sanguis to utilize arginine in addition to carbohydrate as a source of energy may explain why such organisms increase in proportion in the plaque of subjects consuming diets almost devoid of fermentable carbohydrate.

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.

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.

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.

Growth of oral Streptococcus species and Actinomyces viscosus in human saliva.

Microorganisms in dental plaque live in constant association with saliva. The role of saliva in the adherence of bacteria to the teeth and the antibacterial properties of saliva have been well investigated; less interest has been shown in the possible role of saliva as a substrate for oral microorganisms. In this study it was shown that saliva can serve as a growth medium for oral Streptococcus spp. and Actinomyces viscosus. The cell production of these organisms on saliva was carbohydrate limited. The doubling times for growth on glucose-supplemented saliva (4 to 5 mmol/liter) ranged from 1.6 to 4.0 h. The availability of carbohydrate sources for the oral microflora is discussed in relation to microbial growth in the oral cavity.

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)

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.