Meningitis due to a multiply resistant Streptococcus pneumoniae in a child in The Netherlands.
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Biomedical subjects
Publications and source records attributed to C J de Groot.
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Zinc in plasma and urine and serum albumin and alpha 2-macroglobulin were measured in 48 patients with burns. Mean total burned surface area amounted to 18%, ranging from 2 to 55%, and mean hospitalization time amounted to 35 days, ranging from 10 to 124 days. All parameters showed a decrease during the first two post-burn days. Minimal values were reached on days 2 and 3 for plasma and urine zinc, and between days 5 and 10 for the proteins. Thereafter, values increased, rapidly for both plasma and urinary zinc, more slowly for albumin and alpha 2-macroglobulin. The ratio R of the total plasma zinc minus the alpha 2-macroglobulin concentration to the albumin concentration is postulated as an indicator for zinc deficiency. From values of R and of the urinary zinc excretion, conclusions can be drawn about various processes of the zinc metabolism that may occur during the acute stage following the thermal accident and during the stages of tissue demarcation and of recovery. These processes are discussed in terms of possible temporary and/or local zinc deficiency. Evidence is presented that zinc administration in only indicated during the final stages of recovery in case of inadequate dietary intake.
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A cyclophosphamide resistant subline (BNML/CPR) was developed in vivo in the BN rat acute myelocytic leukaemia (BNML) model. Full resistance was achieved after in vivo exposure of leukaemic animals to cyclophosphamide with, in total, 15 intraperitoneal injections of 100 mg/kg. The CPR line was cross-resistant to ifosfamide, but less so to mafosfamide. Continuous transplantation of the BNML/CPR line without a cyclophosphamide selection pressure resulted in the emergence of a subline (BNML/CPR greater than S) whose sensitivity to cyclophosphamide was similar to that of the parent BNML/S line. Both in the BNML parent line and in the BNML/CPR greater than S line, a 2p+ marker chromosome was present, whereas a 2p+q+ marker chromosome was characteristic for the BNML/CPR line. The mechanism of cyclophosphamide resistance can now be investigated in the BNML model at the DNA, at the mRNA and at the protein level.
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At the present, the influence of intrauterine hypothyroidism on the fetus is estimated by bone age (BA). BA is also used as a predictor of later neuropsychologic development. The aim of this study was to investigate whether the neurophysiologic maturation of neonates with congenital hypothyroidism (CHT) is delayed at the start of therapy and, if so, whether this delay is comparable to that in BA. Twenty-seven infants with CHT were examined with median nerve somatosensory evoked potentials (SEP) before or within 1 wk after initiation of therapy. The effect of neonatal jaundice, a potential confounder of neonatal SEP, was also evaluated. Cervical (N13), first cephalic (N19), and second cephalic (N32) peak latencies were measured, as well as N13-N19 interval (central conduction time) and N13 latency divided by arm length. The SEP data of 103 normal infants were used as reference values. In the CHT newborns, a maturational delay was found for all SEP parameters. Preterm infants (n = 3) were conspicuously less affected than term patients. In term CHT infants, jaundice during the first postnatal week, but not late jaundice, had an additional adverse effect. SEP delay was not related to initial or actual T4 levels. BA delay exceeded SEP delay by several weeks. Our data suggest that the depressed T4 levels of the hypothyroid fetus and neonate affect the nervous tissue to a lesser degree than bone tissue and, further, that SEP is superior to BA as parameter for the evaluation of neurologic maturation of infants with CHT.
Almost 50% of the cells infiltrating the central nervous system (CNS) of animals with experimental allergic encephalomyelitis (EAE) are macrophages (M psi). To investigate the role of the M psi in the pathogenesis of EAE, we eliminated M psi by means of mannosylated liposomes containing dichloromethylene diphosphonate (Cl2MDP). Cl2MDP-containing liposomes injected intravenously eliminate M psi in spleen and liver. Incorporation of mannose into the lipid layers enables the liposomes to pass the blood-brain barrier (BBB). Injections of Cl2MDP-containing mannose liposomes intravenously shortly before the appearance of clinical signs, markedly suppressed the expression of clinical signs of EAE. This suppression was accompanied by a marked reduction of infiltrated M psi in the CNS. Cl2MDP-containing liposomes without mannose incorporated had no effect. Cl2MDP-containing mannosylated liposomes had no effect on plasma corticosterone levels compared with injections of saline; thus, the suppression of expression of EAE was not corticosterone mediated. These results show that the M psi within the CNS play an important role in the pathogenesis of EAE.
The results of a longitudinal study on plasma and urine zinc concentrations in a patient with 68 per cent burns are described. Special attention was paid to possible zinc contamination due to the use of bladder catheters for urine sampling. The course of the plasma and urine zinc concentrations during the first 50 days in hospital was comparable to those reported in the literature. It was shown that surgery was associated with a pronounced rise in urine zinc level, while catheter replacement caused no significant increase in urinary zinc content in this particular patient. However, measurements of zinc content of and zinc release from three types of bladder catheters showed that the two types of latex-based catheters contained about 0.25 per cent zinc, versus 0.01 per cent in the siliconelastomer equivalent. During an 8 h perfusion latex catheters released about 1.2 mumols zinc (2.5 mumols/l). Possible errors in urine zinc determinations due to zinc contamination from catheters are calculated. Recommendations are made for minimizing these errors.
The effect of age on the maturation of median nerve somatosensory evoked potentials (SEPs) was studied in 103 normal neonates (24 preterm, 79 term) at the postconceptional age (PCA) of 36-48 weeks. The influence of birth weight was evaluated in 44 term neonates, aged 0-7 days, according to their gestational age (GA) stratified into three groups: A: 38-39 weeks (n = 15); B: 39.5-40.5 weeks (n = 15); C: 41-43 weeks (n = 14). The mean birth weight was not different in the three groups. For all infants the N13 latency recorded at cervical (CS2-Fz) level as well as the N19 onset and peak latency at cortical (C3'/C4'-Fz) level were measured. For these parameters and for the N13 latency divided by arm length (N13/AL) and the N19 ascending time (N19AT) the P50, P97 and P3 were calculated as a function of PCA. They were all decreasing in the 36-48 weeks period, fast before 40 weeks and slowly thereafter. The SEP values of groups, A, B and C were not different, but in each group the wave pattern of the cortical SEPs was more mature in the larger than in the smaller infants. For the groups A, B and C together birth weight (in SDS) correlated inversely with the N13/AL and the N19AT (both in SDS) (r = 0.73 and 0.52 respectively, p less than 0.001). Our data indicate that the progression of maturation of the various SEP components in the period of 36-48 PCA is non-linear.(ABSTRACT TRUNCATED AT 250 WORDS)
Somatosensory evoked potentials (SEPs) were studied in jaundiced and normal neonates on the day the highest bilirubin values were reached, 2-3 days later, and at five weeks. During the first week three groups were formed according to peak bilirubin values: A: greater than or equal to 250 mumol/l (n = 20), B: 125-250 mumol/l (n = 6), C: less than 125 mumol/l or no jaundice (n = 19). At five weeks 10 infants of group A were reinvestigated, together with 17 controls. Cervical (N13) and scalp SEPs (N19) were recorded with a variable number of stimuli. The SEPs of group B and C did not differ from each other. In group A the N13 peak latencies were within the range of group C at the first investigation, but prolonged at the second and third. The cortical components were prolonged at the first investigation, improved but still prolonged at the second, while the N19 peak latency was still prolonged at the third investigation. The central conduction time (CCT) correlated positively with the bilirubin level. Since a rapid decrease in the N19 amplitude was found for all groups from 25 to 100 stimuli, recordings should be done with a low number of stimuli (less than 100). Our findings indicate that both the periferal and the central components of the SEPs in the neonatal period are delayed by jaundice and that full recovery is not obtained at five weeks. The non-invasive SEP technique can be used as a daily monitor of the effect of bilirubin on the CNS.
In this paper we report our studies on the effects of menadione in cultured fibroblasts treated with rotenone to block complex I. A normalization of the lactate to pyruvate ratio after incubation with glucose, an increased production of 14CO2 from [6-14C]glucose and an increased intra-cellular concentration of ATP was observed in the presence of micromolar concentrations of menadione. These results not only demonstrate the potential value of menadione in complex I deficient patients but also suggest that this system can be used advantageously for the in vitro assessment of therapeutic agents for disorders of the mitochondrial respiratory chain.
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Rats suffering from experimental allergic encephalomyelitis (EAE) were examined by a number of investigators whose assessments were compared. Considerable consensus of opinion was reached, especially when a standard, easily interpretable, scoring classification was used. More discrepancies occurred when a more expanded scale, differentiating between more clinical grades, was used. It is demonstrated that part of these discrepancies can be overcome by having the examinations done by the same investigator. Possible consequences of these findings for the assessment of clinical signs in EAE are discussed.
A method has been developed to isolate brain macrophages (M phi) from normal neonatal and adult rats brain cell suspensions, as well as from brain cell suspensions of rat with experimental allergic encephalomyelitis (EAE), by making use of the ability of M phi to adhere to plastic surfaces. The isolated adherent cells were immuno- and enzyme-cytochemically identified. Phagocytic activity and the presence of Fc-IgG receptors were also examined. Approximately 30%-40% of the isolated adherent cells from neonatal rat brain are phagocytic and can be stained with macrophage-specific monoclonal antibodies, suggesting that these cells belong to the monocyte/macrophage lineage. From normal adult rat brain, only a small number of brain M phi could be isolated. A highly purified population of brain M phi was obtained from EAE rat brain. The isolated brain M phi are phagocytic, possess Fc-IgG receptors and rat M phi-associated antigens. Besides these features, the isolated brain M phi also express MHC class II antigens (Ia-antigens), which suggests that M phi may be involved in the regulation of immunological disorders of the CNS. The method reported here for rapidly isolating a large number of blood-monocyte-derived brain M phi from neonatal and adult brain allows an investigation of the precise role of M phi in inflammatory diseases of the central nervous system.
The diagnosis of hypertrophic pyloric stenosis (HPS) with ultrasonography (US) is dependent on measurements of pyloric diameter (PD), pyloric length (PL), and muscle thickness. The authors were unable to confidently diagnose the condition with US in 45% of patients who underwent surgery for HPS because all three criteria were not fulfilled. An overall measurement of the "amount" of pyloric hypertrophy was introduced: pyloric volume (PV), which was equated to 1/4 pi x PD2 x PL. No overlap was found between patients with HPS (n = 22; PV = 3.13 mL; range, 1.4-5.1 mL) and asymptomatic control subjects (n = 28; PV = 0.65 mL; range, 0.2-1.3 mL) or symptomatic subjects without HPS (n = 25; PV = 0.86 mL; range, 0.4-1.3 mL). A positive correlation was found between age at diagnosis and PV, a finding reflecting that HPS is an acquired condition. In patients less than 4 weeks of age, the criterion of PV greater than or equal to 1.4 mL proved to aid in the identification of early HPS more accurately than any existing criteria.
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Experimental allergic encephalomyelitis (EAE) in Lewis rats is an acute monophasic autoimmune disease. It can be treated prophylactically and therapeutically with high doses of cyclosporin A (CsA). Here we demonstrate that low-dose CsA does not prevent a first attack of EAE, but, on the contrary, induces a chronic relapsing form of the disease in 100% of Lewis rats examined. Possible explanations for the high relapse rate after low-dose CsA treatment are discussed. Further studies will be needed to evaluate the immunological mechanisms responsible for these results.
The central nervous system (CNS) contains several types of neuroglial cells. In the present study, we characterized different types of glial cells in rat CNS by using single and combined immuno- and enzyme-histochemical methods, and immunofluorescence techniques. Two recently developed monoclonal antibodies (mAbs) against rat macrophages-associated antigens appeared to recognize a subpopulation of glial cells in the CNS of normal adult rats. These ED4- and ED8-positive glial cells were predominantly located in the white matter of adult rat CNS and shared morphological features with microglia. ED4 and ED8 were applied in a double staining combined with mAbs and an antiserum raised against galactocerebroside (GalC) to identify oligodendrocytes, or with anti-glial fibrillary acidic protein antiserum (GFA) to identify astrocytes. We also used a mAb against myelin basic protein (MBP) to identify oligodendrocytes. It appeared that ED4 and ED8 recognized a subpopulation of oligodendrocytes. MAbs against GalC and MBP recognized cells in an immunoperoxidase staining with a morphology identical to that of the ED8-positive cells and part of the ED4-positive cells. Frozen sections of Lewis rats CNS with acute experimental allergic encephalomyelitis (EAE) were investigated, where infiltrating brain macrophages could be found which stained positively with ED4 and ED8 as well as with the monocyte/macrophage mAbs ED1 and ED2. These brain macrophages did not stain when GalC, MBP and GFA markers were applied. Furthermore, ED4+GalC+ and ED8+GalC+ oligodendrocytes were present in the CNS white matter of EAE animals with similar appearance as in normal adult rats. With the currently used markers, we could not detect a third type of neuroglial cell, besides the astrocytes and oligodendrocytes. Thus, none of our anti-macrophage monoclonals recognized the presumptive microglia. Only under pathological conditions, e.g., in inflammatory infiltrates in the course of EAE, could brain macrophages be detected in the CNS parenchyma and only in the direct vicinity of blood vessels, indicating their hematogenous origin.