Laboratory screening for side effects of disease modifying antirheumatic drugs in daily rheumatological practice.

To observe the actual laboratory screening for side effects of disease modifying antirheumatic drugs (DMARDs) in daily rheumatological practice, a retrospective multi-center cohort study was performed on the laboratory tests in DMARD treated rheumatoid arthritis (RA) patients. RA patients were investigated by chart review if they started with a DMARD (cohort 1) or were treated with a DMARD for at least one year (cohort 2). Hematological, hepatic, and renal tests were collected. In cohort 1 and 2, 513 and 1209 patients were included, respectively. A fairly outlined screening profile was observed for each DMARD studied. Except for antimalarials, the testing frequency decreased with time in cohort 1. For all DMARDs the testing frequency in cohort 1 was higher than in cohort 2. In general, rheumatologists requested laboratory tests less frequently than is internationally recommended. This discrepancy raises questions about the relation between the efficacy and costs of laboratory screening for side effects of DMARDs in patients with RA.

[Twenty years of childhood coeliac disease in the Netherlands: more diagnoses and a changed clinical picture]. / Twintig jaar coeliakie bij kinderen in Nederland: meer diagnosen en een veranderde verschijningsvorm.

OBJECTIVE: To assess the incidence of childhood coeliac disease in the Netherlands and to study the clinical features. DESIGN: Prospective. SETTING: Leiden University Medical Centre, Leiden, the Netherlands. METHOD: Cases of childhood coeliac disease in the Netherlands in 1993-1995 were identified by means of the Dutch Paediatric Surveillance Unit. Inclusion criteria were: birth in the Netherlands, diagnosis with at least one small bowel biopsy in 1993-1995 and age at diagnosis 0-14 years. The data were cross checked with the Dutch Network and National Database of Pathology and compared with data from a previous study on childhood coeliac disease, 1975-1990. RESULTS: 297 Coeliac patients were identified by means of the Surveillance Unit, another 32 through the National Database of Pathology. The mean crude incidence rate of diagnosed childhood coeliac disease was 0.51/1000 live births, which was in the range of rates found in other West European countries and significantly higher than the mean crude incidence rate of 0.18/1000 live births found in the Netherlands in 1975-1990. The clinical presentation was classic up to 1990: chronic diarrhoea, abdominal distention and growth failure. From 1993 onward, however, the number of children with chronic diarrhoea and abdominal distention decreased significantly and the number with weight loss, anaemia and abdominal pain increased. Associated disorders were present in 13.7% of the cases. CONCLUSIONS: The incidence of diagnosed childhood coeliac disease in the Netherlands showed a tendency to increase significantly during the past decade. In a period of 20 years a significant trend toward change in the clinical presentation of coeliac disease in Dutch children was observed.

Twenty years of childhood coeliac disease in The Netherlands: a rapidly increasing incidence?

BACKGROUND: The incidence of coeliac disease varies internationally. AIMS: To assess the incidence of childhood coeliac disease in The Netherlands and to study the clinical features and the presence of associated disorders. SUBJECTS: Identified cases of childhood coeliac disease in The Netherlands in 1993-4 by means of the Dutch Paediatric Surveillance Unit. METHODS: Inclusion criteria were born in The Netherlands, diagnosed with at least one biopsy of the small bowel in 1993-4 and age at diagnosis 0-14 years. The data were cross checked by the Dutch Network and National Database of Pathology and compared with data from a previous study on childhood coeliac disease, 1975-90. RESULTS: A total of 193 coeliac patients were identified by means of the Surveillance Unit, another 20 through the National Database of Pathology. The mean crude incidence rate of diagnosed childhood coeliac disease was 0.54/1000 live births, which is in the range of rates found in other western European countries and significantly higher than the mean crude incidence rate of 0.18/1000 live births found in The Netherlands in 1975-90. The clinical presentation was classic: chronic diarrhoea, abdominal distension, and growth failure. Associated disorders were present in 11.7% of the cases. CONCLUSIONS: The incidence of diagnosed childhood coeliac disease in The Netherlands seems to have increased significantly during the past few years. In a period of 20 years no significant changes could be found in the clinical picture at preentation of coeliac disease in Dutch children.

A comparative study of isolated liver perfusion versus hepatic artery infusion with mitomycin C in rats.

Systemic toxicity is usually the dose-limiting factor in cancer chemotherapy. Regional chemotherapy is therefore an attractive strategy in the treatment of liver metastasis. Two ways of regional chemotherapy, hepatic artery infusion (HAI) and isolated liver perfusion (ILP), were compared investigating the difference in toxicity with tissue and biofluid concentrations of mitomycin C (MMC). In wistar derived WAG rats the maximally tolerated dose of mitomycin C via HAI was 1.2 mg kg-1. Body weight measurements after HAI with doses higher than 1.2 mg kg-1 suggest both an acute and delayed toxic effect of mitomycin C since the time weight curves were triphasic: a rapid weight loss, a steady state and a second fall in weight phase. These rats died due to systemic toxicity. ILP with 4.8 mg kg-1 was associated with no signs of systemic toxicity and only transient mild hepatotoxicity. ILP with 6.0 mg kg-1 was fatal mainly due to hepatic toxicity. The four times higher maximally tolerated dose in ILP resulted in a 4-5 times higher peak concentration of mitomycin C in liver tissue, while the plasma concentration remained significantly lower than in the HAI treated rats. In the tumour tissue a 500% higher concentration of mitomycin C was measured in the ILP with 4.8 mg kg-1 than in HAI with 1.2 mg kg-1 treated rats. We demonstrated that when mitomycin C was administered by ILP a 400% higher dose could be safely administered and resulted in a five times higher tumour tissue concentration. In view of the steep dose-response curve of this alkylating agent this opens new perspectives for the treatment of liver metastasis.

Time trends and survival in patients presented for surgery with non-small-cell lung cancer 1969-1985.

All evaluable patients (n = 920) with primary non-small-cell lung cancer (NSCLC) who were presented for surgery in our hospital between 1969 and 1985 were reviewed as to histological findings, postoperative stage, age group and surgical procedure. Time trend analyses showed a significant increase over time in the proportion of adenocarcinomas (p = 0.025) and in the proportion of the elderly (greater than or equal to 70 years; p = 0.014). The 5-year survival rates by year of operation showed no improvement at all over time; on the contrary they showed a decline, which however only reached significance for patients who underwent pneumonectomy (p = 0.034). It is noted that the overall survival curves up to 5 years showed no significant differences between patients with adenocarcinoma and patients with squamous cell carcinoma, or between patients aged 70 years or more and patients aged 60-69 years. Despite expanded preoperative diagnostic techniques and developments in surgical treatment, no improvement in the survival after surgery for NSCLC over the period 1969-1985 could be established.

Diabetes mellitus type I. Results of a European questionaire.

An anonymous questionaire concerning diabetes type I was circulated through (Young) AEMIE members. Questions were asked regarding available facilities, diagnosis, follow-up and therapy. One hundred and six completed questionaires were available for study: most were from 5 countries, i.e. 20 from the Netherlands (NL), 26 from Great Britain (GB), 16 from France (F), 16 (+2) from Belgium (B) (+ Luxemburg = LUX) and 19 from Ireland (IRL). There was a preponderance of general internists and internist/diabetologists. In Great Britain significantly more participants were internist/diabetologists and they treated significantly more patients than other participants. They also had access to more facilities, especially diabetes nurses. Most patients appeared to perform bloodglucose measurements; only 10 p. 100 of the patients did not measure glucose in blood or urine at all. There is general acceptance that bloodglucose regulation should be as tight as possible. The allowance of sugar under certain conditions was mostly permitted in the Benelux countries. The use of insulin pens exceeded that of insulin pumps. The preference for pens was primarily related to convenience for patient and doctor and low cost. The main indication for their use was bad regulation. This study confirms the impression that there is an increased interest in patient education (i.e. diabetes nurses, educational programmes and home blood glucose monitoring) amongst European physicians and a trend towards using new devices such as insulin pens and pumps in an effort to achieve a tighter blood sugar control.

Comparative recovery of Streptococcus mutans on five isolation media, including a new simple selective medium.

For the isolation of Streptococcus mutans, several selective media have been developed, of which Mitis-Salivarius Sucrose Bacitracin agar (MSB) is the most widely used (Gold et al., 1973). Recently, the Trypticase Yeast-Extract Cystine agar medium (TYC, de Stoppelaar et al., 1967) was modified into a selective medium for S. mutans, called Trypticase Yeast-Extract Cystine Sucrose Bacitracin (TYCSB, van Palenstein Helderman et al., 1983). The aim of this study was to compare the recovery of S. mutans from clinical samples on Mitis-Salivarius agar (MS), MSB, TYC, and TYCSB. Further, a new simple selective medium for S. mutans was introduced. This medium, called TSY20B, was supposed to have the same qualities as TYCSB, but its preparation is less laborious. One hundred eighty-five plaque and saliva samples from 37 subjects were plated on MS, MSB, TYC, and TYCSB, and 285 samples from 23 subjects were plated on TYCSB and TSY20B. All plates were incubated at 37 degrees C in a 91% N2, 5% CO2, 4% H2 atmosphere for five days. The S. mutans counts on TYC and TYCSB were significantly higher than on MS or MSB by almost a factor of 10. Seventy-seven percent of the samples gave higher S. mutans counts on TYCSB than on MSB. Especially, samples with high S. mutans d/g numbers gave lower S. mutans counts on MSB. These data clearly indicate that MSB agar is inhibitory for S. mutans and should not be used. An additional advantage of TYCSB over MSB agar is the possibility of distinguishing S. mutans serotypes d/g from other serotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Effect of fluoride on growth and acid production by Streptococcus mutans in dental plaque.

The aim of this study was to measure the effect of fluoride on the production of organic acids by Streptococcus mutans in dental plaque. The effect was studied in a simplified model of dental plaque with gnotobiotic rats monoinfected with S. mutans Ny341. Adaptation of S. mutans to fluoride was induced by feeding one group of the rats on fluoride-containing diet and drinking water. No difference was found in the accumulation of S. mutans on the teeth between the fluoride-adapted and the control groups. However, there was a significant difference in the amount of lactic acid in metabolically resting plaque between the groups, lactic acid being lower in the fluoride-adapted plaque. At 5 min after a rinse containing 10% sucrose, a high level of lactic acid was found in plaque from animals not exposed to fluoride. Rinses containing 4 or 20 mM fluoride before the sucrose rinse significantly inhibited the lactic acid production in the control group. In the plaque from rats on fluoridated diet and drinking water the sucrose-induced production of lactic acid was not inhibited by a 4 mM fluoride rinse. Moreover, the production of lactic acid in the fluoride-adapted plaque was prolonged. The results indicate that due to fluoride adaptation the inhibition of acid production is unlikely to be important for the caries-preventive action of fluoride.

Analysis of bacterial fermentation products by isotachophoresis.

Various carboxylic acids from bacterial fermentation could easily be separated by isotachophoresis. The analyses were performed on an LKB 2127 Tachophor, and under the conditions used the minimum amount of sample that could be quantitatively estimated was approximately 0.1 nmol. The reproducibility of the method was good (ca. 5 percent). The time of analysis using a 23-cm column was 12 min. No pretreatment of the samples was required.