Centenary of the Health Council of the Netherlands. IV. Infectious diseases

Many advisory reports of the Health Council of the Netherlands in the past century have dealt, directly or indirectly, with infectious diseases. One example is vaccination against smallpox. At the start of the last century, advice on this subject was important: initially, vaccination was compulsory by law, but people became increasingly aware of the associated side effects. A second example is immunisation against acute anterior poliomyelitis, which became a reality during the fifties. The advice also contained a discussion of which vaccine should be chosen: the inactivated 'dead' (Salk) form or the attenuated 'live' form (Sabin). Due to sound national organisation and associated logistics, a high level of vaccination was (and still is) achieved and the clinical disease known as polio disappeared from the Netherlands. Food-borne infections form the third example. The effect of the advice published by the Council on this subject (from 1960 onwards) has been limited, for a large part due to the significant economic consequences of the proposals for beef farming. The developments in the field of infectious diseases, immunology and vaccinology, together with social developments make it likely that in the coming years the Council will also frequently be asked for advice in the field of infectious diseases and the fight against them.     

The performance of two rapid quantitative D-dimer assays in 287 patients with clinically suspected pulmonary embolism

Context: Objective tests are necessary for the diagnosis of pulmonary embolism (PE). D-dimer assays have been suggested as useful screening tests to exclude this diagnosis. Objective: To compare the diagnostic accuracy of two rapid quantitative D-dimers in patients with suspected pulmonary embolism. Design: Plasma D-dimer levels were measured using two commercially available assays (Tinaquant® and Vidas®). A strict imaging protocol was used to arrive at a final diagnosis of PE or deep venous thrombosis (DVT). Setting: Multicenter study in six Dutch referral centers. Patients: A total of 287 in- and outpatients with clinically suspected pulmonary embolism. Main outcome measures: Diagnostic accuracy indices for the two assays were calculated and additional receiver-operated characteristics (ROC) analysis was performed. Results: Using the manufacturer's advised cutoff values, the sensitivity and specificity were 88% and 52% for Vidas and 82% and 61% for Tinaquant, respectively. These differences were statistically significant (McNemar, P<0.0001). However, no statistical differences were found between the two assays using ROC analysis (AUC=0.78 for both assays). Conclusions: Both quantitative D-dimer tests had similar diagnostic accuracy; however, at the manufacturer's advised cutoff level, Vidas performed significantly better. Nevertheless, to safely exclude pulmonary embolism, D-dimer assays should be combined with other diagnostic tests.     

Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors.

PURPOSE: To investigate the feasibility and pharmacokinetics of the combination cisplatin, gemcitabine, and SU5416. PATIENTS AND METHODS: Patients received cisplatin 80 mg/m(2) on day 1, gemcitabine 1,250 mg/m(2) on days 1 and 8, repeated every 3 weeks, and SU5416 (85 and 145 mg/m(2)) intravenously twice weekly. Pharmacokinetics of all three agents, side effects, and antitumor response were investigated in patients with solid tumors amenable to therapy with cisplatin/gemcitabine. RESULTS: In the first cohort of three patients entered at the 85 mg/m(2) dose, no dose-limiting toxicities were observed. In the next cohort (145 mg/m(2)), three patients developed a thromboembolic event. After entry was restricted to patients with low thromboembolic risk, three additional patients enrolled at 145 mg/m(2) developed a thromboembolic event. The dose was then reduced to 85 mg/m(2) in all patients still on the study, and three additional patients were entered on this dose level. In 19 treated patients, eight patients developed nine thromboembolic events (three transient ischemic attacks, two cerebrovascular accidents, and four deep venous thromboses). The most common toxicities observed were those previously reported for SU5416 alone (headache and phlebitis) and for this chemotherapy regimen (nausea, thrombocytopenia, and leucopenia). No significant pharmacologic interaction among the three drugs was observed. Response rates were similar to those expected in the patient population selected for this study. Analysis of variables of the coagulation cascade and of vessel wall activation was performed in three patients and showed significant increases in thrombin generation and endothelial cell perturbation in a treatment cycle-dependent manner. CONCLUSION: The incidence of thromboembolic events, possibly related to the particular regimen tested in this study, discourages further investigation of this regimen.     

Post-radiotherapy contrast enhancement changes in fast dynamic MRI of cervical carcinoma

This pilot study determines fast dynamic gadolinium enhanced MRI contrast enhancement parameters (onset of enhancement and time to peak enhancement) before and after radiotherapy in 10 cervical carcinoma patients. Before radiotherapy, onset of enhancement and time to peak enhancement were early, with a median of 4.5 and 5.2 seconds, respectively. High-grade tumors showed early enhancement, compared with low-grade. After radiotherapy, contrast enhancement patterns differed. In survivors, onset of enhancement after radiotherapy was later than before radiotherapy. In non-survivors, onset of enhancement after radiotherapy was still early. The median difference in onset of enhancement before and after radiotherapy in survivors and non-survivors was an increase of 3.2 and a decrease of 1.1 seconds, respectively. Early onset of enhancement after radiotherapy was a better predictor for survival than a high-signal intensity zone on post radiotherapy unenhanced T1/T2-weighted MRI. It is concluded that enhancement parameters from fast dynamic Gd-enhanced MR images can provide additional functional information with regard to tumor vascularization, and may have prognostic significance. It complements clinical examination and unenhanced MRI in determining the effectiveness of radiotherapy treatment in cervical carcinoma. Future studies will focus on the clinical utility and improvements of the estimation of contrast-enhanced parameters with this new technique.     

Ductus Arteriosus Doppler in der ersten Schwangerschaftshälfte

Zusammenfassung Zusammenfassend stellen wir fest, da? es m?glich ist, Flu?geschwindigkeiten durch den ductus arteriosus ab der 11. SSW zu messen. Enddiastolischer Flow tritt an der 13. SSW auf, vermutlich aufgrund abnehmender Afterload. Sowohl eine Abnahme der peripheren Afterload (Plazenta) als auch eine Zunahme der rechtsventrikul?ren Kontraktilit?t und das Auswurfvolumen sind für den Anstieg aller Blutflu?geschwindigkeiten im ductus arteriosus verantwortlich.     

Phenylketonuria and some aspects of emotional development

Early dietary treatment of phenylketonuria (PKU) prevents intellectual retardation and gross neurological impairment although not all neuropsychological problems. This study investigates to what extent the illness and its treatment imposes a burden on emotional development of early-treated PKU patients and on rearing practices of their parents. It is concluded that in early-treated PKU it is particularly difficult to find constructive ways to adapt to the situation for children as well as for parents. As coping with PKU and its treatment is so complicated, paediatric control should be combined with psychocounselling.     

Lateral dural sinus thrombosis in childhood

OBJECTIVES: To present etiology, diagnosis, and treatment of dural sinus thrombosis (DST) in children. To discuss the diagnostic role of contrast-enhanced computed tomography (CECT) and to evaluate the controversial treatment modalities of anticoagulation, surgical drainage of the infected sinus, and ligation of the internal jugular vein (IJV). STUDY DESIGN: Retrospective chart review and analysis of computed tomography (CT) scans and follow-up visits to document the clinical outcome. METHODS: Between 1986 and 1996, CT scans of 15 children revealed DST. These patients were further investigated. RESULTS: The etiology could be divided in three groups: group A, infection (6); group B, trauma (6); and group C, coagulation disorders. There were neither symptoms nor clinical findings specifically related to DST but rather, these were related to the underlying disease or condition (otitis media, skull base fractures). Diagnosis was made by CECT in all cases. Fusobacterium necrophorum was found in 4 of 6 patients in group A. Early mastoidectomy with incision and drainage of the thrombosed sigmoid sinus was performed in patients in group A. Postoperative intravenous (IV) heparin was given; however, no ligation of the IJV became necessary. In all patients in group C, protein C or protein S deficiency, or both, was detected. CONCLUSIONS: CECT with adequate window-level settings allows the diagnosis of a DST with high sensitivity. Treatment of choice for septic DST consists of administration of antibiotics and early surgical drainage. We recommend anticoagulation therapy in children with septic DST during their hospitalization.     

Characterization of abnormalities in the gamma-globin gene arrangements of Japanese newborns

Cord blood samples from 889 healthy Japanese newborns from three districts of Honshu Island were studied with the purpose of characterizing the gamma-globin genes in the Japanese. The A gamma T gene frequency was 0.159 which is the same as that found elsewhere in Japan. The haplotype of the chromosome with the A gamma T gene was [-- ++ - + (+ or -) (+ or -)] at eight polymorphic sites. Data from analyses of DNA and the proportion of gamma chains in Hb F showed the existence of various kinds of gamma-globin gene arrangements; six genotypes were observed for individuals with high G gamma values and triple or quadruple gamma-globin gene arrangements, and seven genotypes for babies with low G gamma values and a single gamma-globin gene. The in vivo expression of the gamma-globin gene located at the third or fourth position in the multiple gene arrangement was found to be about 5% and 2.5% of the total, respectively. The haplotype for the chromosomes with a triple gamma-globin gene was [+ --(-)---- +], but that for the chromosomes with a single gamma-globin gene remains unclear. In addition, a new type of Bgl II polymorphism in the G gamma-globin gene was observed.