Children referred for specialist care: a nationwide study in Dutch general practice.

BACKGROUND: Insight into referral patterns provides general practitioners (GPs) and specialists with a frame of reference for their own work and enables assessment of the need for secondary care. Only approximate information is available. AIM: To determine how often, to which specialties and for what conditions children in different age groups are referred, as well as how often a condition is referred given the incidence in general practice. METHOD: From data of the Dutch National Survey of Morbidity and Interventions in General Practice, 63,753 new referrals (acute and non-acute) were analysed for children (0-14 years) from 103 participating practices (161 GPs) who registered. Practices were divided into four groups. Each group of practices participated for three consecutive months covering a whole year altogether. We calculated referral rates per 1000 children per year and referability rates per 100 episodes, which quantifies the a priori chance of a condition being referred for specialist care. RESULTS: The referral rate varied by age from 231 for children under 1 year old to 119 for those aged 10-14 years (mean 159). The specialties mainly involved were ENT, paediatrics, surgery, ophthalmology, dermatology and orthopaedics. Referrals in the first year of life were most frequently to paediatricians (123); among older children the referral rate to paediatricians decreased (mean 36). Referrals to ENT specialists were seen particularly in the age groups 1-4 (71) and 5-9 (53). For surgery, the referral rate increased by age from 19 to 34. Differences between boys and girls were small, except for surgery. The highest referral rates were for problems in the International Classification of Primary Care (ICPC) chapters: respiratory (28); musculoskeletal (25); ear (24) and eye (21). Referability rates were, in general, low for conditions referred to paediatrics and dermatology and high for surgery and ophthalmology. The variation in problems presented to each specialty is indicated by the proportion of all referrals constituted by the 10 most frequently referred diagnoses: from 35% for paediatrics to 81% for ENT; for ophthalmology, five diagnoses accounted for 83% of all referrals. CONCLUSIONS: The need for specialist care in childhood is clarified with detailed information for different age categories, specialties involved and variation in morbidity presented to specialists, as well as the proneness of conditions to be referred.     

The prevalence of A. actinomycetemcomitans, P. gingivalis and P. intermedia in selected subjects with periodontitis

Abstract. The present study was carried out in a private periodontal practice. 8 clinical criteria were chosen to select patients for microbiological examination. These criteria characterize prominent features of disease which at the start, during, or in the maintenance phase of treatment suggest difficulties in the progress of the periodontal therapy. Based on these clinical characteristics, an inventory was made of the prevalence of the 3 putative periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia. Out of 320 referred patients 91 patients did meet 1 of the clinical criteria and consequently were selected for microbiological examination. Results showed that young patients (19–30 years) with periodontitis demonstrated the presence of A. actinomycetemcomitans more often (69%: p (0.005) compared to older age cohorts. A. actinomycetemcomitans was found more often when localized breakdown (in particular in the 1 st molar and incisor region) was observed and in patient who responded poorly to scaling and rootplaning. P. gingivalis and P. intermedia were most frequently recovered in patients showing primarily a bone loss pattern of angular defects of 5 mm. Retrospectively, these patients were further categorized, based on full mouth radiographs, in (1) patients with primarily horizontal bone loss and (2) patients with primarily angular bony defects. Results showed that A. actinomycetemcomitans occurred less frequently in patients showing horizontal bone loss ( p (0.05).     

A frequent thrombomodulin amino acid dimorphism is not associated with thrombophilia.

We report a C/T dimorphism in the thrombomodulin (TM) gene that predicts an Ala455----Val replacement in the sixth EGF-like domain of TM. This dimorphism has allelic frequencies of 82 (Ala) and 18% (Val) in a normal population. In a group of protein C deficient patients and in a group of subjects with unexplained thrombophilia the allelic frequencies were found to be the same as in the normal population. This indicates that with respect to thrombophilia the dimorphism is essentially neutral.     

Dentists' opinions of their dental education; results of a survey of dentists who studied in Amsterdam between the years 1982-1990

Four hundred and fifty dental graduates from the Free University (VU), the University of Amsterdam (UvA) or the Academic Center for Dentistry Amsterdam (ACTA) between 1982 and 1990 were asked by questionnaire to give their opinion about the undergraduate dental training they received. Most respondents felt that their undergraduate education prepared them reasonably well for general practice. Yet imperfections in the education were noticed. These imperfections show resemblance to conclusions from similar surveys in other countries.     

Post-tetanic potentiation increases energy cost to a higher extent than work in rat fast skeletal muscle

We studied the effects of (post-tetanic) potentiation on myosin light chain (MLC-2) phosphorylation, work and energy cost in skeletal muscle. Experiments were performed using in situ medial gastrocnemius muscles of male Wistar rats, which were electrically stimulated through the severed sciatic nerve. One group of muscles was first potentiated with an isometric tetanus before a series of 10 concentric contractions (PRC). A second group performed the same series of contractions without previous potentiation (RC). Following the last contraction the muscles were rapidly frozen and excised after which the high-energy phosphate content, lactate concentration and the level of MLC-2 phosphorylation were measured. The results indicate that PRC muscles had a higher (P < 0.05) total work output 144.5 ± 17.0 (SD) (n = 6) vs. 121.6 ± 11.4 (SD) (n = 6) mJ and level of MLC-2 phosphorylation (49.2 ± 7.3 vs. 40.8 ± 3.6%) than RC muscles. The energy cost of the series of concentric contractions in the PRC muscles (9.8 ± 1.9 μmol∼P/muscle) was significantly higher (P < 0.05) than the energy cost in the RC muscles (6.2 ± 0.97 μmol∼P/muscle). It was shown that the relative increase in energy cost of PRC muscles was higher (P < 0.05) than in total work output. It is proposed that the relative high increase in energy cost is the direct result of the increase in muscle performance rather than a property of potentiation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Brown and Eccles'' Depiction of Vagal Effects: An Old and Widely Used Method Reexamined

It can be shown that the procedure for representing the effect of the vagal innervation of the heart introduced by Brown and Eccles in 1934 distorts the actual course of the inhibitory effect. A corrected procedure is proposed. It is stressed that cycle phase specificity of the stimulation can be studied only by drawing different curves representing the course of the vagal effect for different times of stimulation within the cardiac cycle.     

Perceptual Performance as a Function of Intra-Cycle Cardiac Activity

The purpose of the experiment was to test the hypothesis of a systematic change in perceptual performance within a single cardiac cycle due to the activity of the baroreceptors in carotid sinus. As an index of perceptual performance the d_s-parameter from signal detection theory (TSD) was used. A 1000 Hz sine tone had to be detected in a background of white noise. Each of 4 subjects received on the average 4605 noise or noise plus tone stimuli distributed over 10 experimental sessions. When comparing performance during time intervals before and after baroreceptor activity onset no significant difference was found. Also, when tracing perceptual performance over the whole cardiac cycle in steps of 66,100, and 200 msec, no systematic variation could be detected. For steps of 33 msec a rhythmic pulsation of perceptual performance of about 8 Hz appeared. An influence of electrical activity of the brain on perceptual performance was postulated. This activity would have to be time-locked to carotid sinus baroreceptor activity.     

Salmonella pathogenicity island 1-independent induction of apoptosis in infected macrophages by Salmonella enterica serotype typhimurium

The enteric pathogen Salmonella enterica serotype Typhimurium induces apoptosis in infected macrophages. This process is rapid, specific, and depends on the type III protein secretion system encoded within Salmonella pathogenicity island 1 (SPI1). Here, we demonstrate that serotype Typhimurium can activate programmed macrophage cell death independently of SPI1. SPI1 independent induction of apoptosis in infected macrophages is observed as early as 12 to 13 h postinfection, even in the absence of intracellular bacterial replication. Delayed activation of programmed macrophage cell death is not observed with serotype Typhimurium strains mutated in ompR or SPI2. Even though SPI2 mutants have a defect in intracellular proliferation, our results indicate that long-term intracellular survival and growth are not required for delayed macrophage killing per se, since Salmonella mutants that are severely defective in intracellular growth still induce delayed apoptosis. Inactivation of genes required for either rapid or delayed induction of apoptosis results in a conditional noncytotoxic phenotype, whereas simultaneous inactivation of genes required for both rapid and delayed induction of apoptosis renders serotype Typhimurium noncytotoxic under all conditions tested. Our hypothesis is that differential activation of programmed macrophage cell death by serotype Typhimurium occurs under discrete physiological conditions at distinct locations within an infected host.     

High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin (Mylotarg) treatment in acute myeloid leukemia patients.

Gemtuzumab ozogamicin (Mylotarg) induces remission in approximately 30% of relapsed AML patients. We previously demonstrated that gemtuzumab infusion results in near-complete CD33 saturation in peripheral blood, and that saturating gemtuzumab levels result in continuous binding and internalization of gemtuzumab due to renewed CD33 expression. We now demonstrate that a high CD33-antigen load in peripheral blood is an independent adverse prognostic factor, likely due to peripheral consumption of gemtuzumab. Indeed, CD33 saturation in bone marrow is significantly reduced (40-90% saturation) as compared with CD33 saturation in corresponding peripheral blood samples (>90%). In vitro, such reduced CD33 saturation levels were strongly related with reduced cell kill. Apparently, high CD33-antigen loads in blood consume gemtuzumab and thereby limit its penetration into bone marrow. Consequently, CD33 saturation in bone marrow is reduced, which hampers efficient cell kill. Therefore, gemtuzumab should be administered at higher or repeated doses, or, preferably, after reduction of the leukemic cell burden by classical chemotherapy.     

High incidence and unique features of antigen receptor gene rearrangements in TEL-AML1-positive leukemias.

The t(12;21) translocation resulting in the TEL-AML1 gene fusion is found in 25% of childhood B-cell precursor (BCP) acute lymphoblastic leukemias (ALL). Since TEL-AML1 has been reported to induce cell cycle retardation and thus may influence somatic recombination, we analyzed 214 TEL-AML1-positive ALL by PCR for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. As a control group, 174 childhood BCP ALL without a TEL-AML1 were used. The majority of TEL-AML1-positive leukemias had a higher number of Ig/TCR rearrangements than control ALL. They also had a more mature immunogenotype characterized by their high frequency of complete IGH, IGK-Kde, and TCRG rearrangements. While IGK-Kde and TCRG were more frequently rearranged on both alleles at higher age, IGH and TCRD rearrangements decreased in their incidence along with a decrease in biallelic IGH rearrangements. This suggests that the recombination process continues in these leukemias leading to ongoing rearrangements and possibly also deletions of antigen receptor genes. We here provide first evidence that somatic recombination of antigen receptor genes is affected by the TEL-AML1 fusion, and that further age-related differences are probably caused by the longer latency period of the prenatally initiated TEL-AML1-positive leukemias in older children.