Ultrastructural studies in Jacob-Creutzfeldt disease.
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Biomedical subjects
Publications and source records attributed to M Weiss.
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A unique definition of the apparent volume of distribution at steady-state is presented which is consistent with the realistic concept of blood concentration differences within the circulatory system. A physiologically based pharmacokinetic model consisting of eliminating and non-eliminating organs is used to predict the effect of drug elimination upon the steady-state distribution volume.
Based on a two-compartment organ model the total exposure in a target tissue, the mean tissue residence time and the peak time of the tissue concentration are evaluated in terms of tissue to blood partition coefficient and permeability coefficient (membrane permeability) of the drug, as well as the organ volume and blood flow. The total exposure is dependent upon the partition coefficient whereas the mean residence time is also affected by the permeability coefficient of the target organ. The peak time of tissue concentration following bolus intravenous injection appears to be mainly determined by the mean organ transit time and the time course of blood concentration. A tissue specific therapeutic ratio is defined using the concept of total exposure and the advantages of a local route of drug administration are discussed in this respect.
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A model of metabolite pharmacokinetics is developed in terms of residence time distributions and derived non-compartmental measures. It provides quantitative insight into factors determining the concentration-time curve of metabolite following intravenous and oral administration of the precursor drug. The AUCs and higher curve moments (mean residence times and relative dispersions) are calculated/predicted and their dependence on mean absorption time, fraction of first-pass metabolism and intrinsic disposition residence times of the parent drug and metabolite, respectively, is discussed. An AUC-based method for the determination of the first-pass effect is proposed which is not influenced by drug absorption. The approach is valid for linear pharmacokinetic systems exhibiting hepatic and renal elimination of the precursor drug; it is not restricted to specific compartmental models. Limitations of previous concepts of metabolite kinetics are defined. Criteria are presented for the appearance of concave metabolite curves in a semi-logarithmic scale.
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Clinical staging of supraglottic carcinoma requires evaluation of the pre-epiglottic space (PES). To explore the role of fine needle aspiration biopsy of the PES in the staging of epiglottic carcinoma, endoscopic transvallecular fine needle aspiration biopsies of the PES were performed in 16 patients with epiglottic carcinoma. The results of aspiration cytology were compared with CT scanning and postoperative histopathologic sections of the PES after total or supraglottic laryngectomy. This preliminary report shows that needle aspiration biopsy of the PES is a safe and sensitive technique, having a high correlation with histopathologic follow-up. Needle biopsy, along with CT scan, is clinically useful in staging the PES, which cannot be examined directly.
Using the enzyme-linked immunosorbent assay (ELISA), we studied the IgG and IgM antibody titers in various groups of pediatric patients (n = 81) infected with gram-negative organisms. Unlike the control group (n = 12), IgG antibodies were detected in only five (all under four months of age) of 19 children with sepsis. We assume that either the IgG antibodies are used up during the infection, or the lack of IgG antibodies results in a disposition to sepsis; the latter is more probable. Seventeen of 18 patients with urinary tract infections and proven renal involvement were IgM-positive. This indicates a permanent antigen stimulus, possibly in the form of a fixed antigen complex. Because of the heterogeneity of the groups studied, no overall statements can be made for the 93 children studied, some of whom were studied repeatedly. These children included 17 with tracheal colonization, 17 with recurrent urinary tract infections without proven renal changes and six with wound infections.
Two different receptors exist for tumor necrosis factor-alpha (TNF-alpha), designated as p55 (TNF-RI) and p75 (TNF-RII). Soluble (= s) forms of TNF-Rs are secreted after proteolytic cleavage and block the effects of TNF-alpha. sTNF-RI, sTNF-RII and the soluble interleukin 2 receptor (sIL-2R) were determined by ELISA in serum samples of HIV-infected children and adolescents. Twelve children with vertical HIV infection (mean age +/- SD, 5.9 +/- 3.8 years) and 17 horizontally infected patients (16.1 +/- 7.3 years) were classified according to the revised CDC criteria. Twenty healthy control persons (6.4 +/- 5.8 years) showed the following receptor concentrations (median): sTNF-RI 888 pg/ml, sTNF-RII 1,741 pg/ml, sIL-2R 94 pM. Compared to controls, horizontally HIV-infected patients had significantly (Mann-Whitney U test) higher levels for sTNF-RI (median 1,192 pg/ml), sTNF-RII (3,481 pg/ml) and sIL-2R (128 pM). For vertically infected children only sTNF-RII (2,944 pg/ml) was significantly elevated compared to controls. There were no differences in soluble receptor levels between vertical or horizontal transmission. Surprisingly, no significant differences for sTNF-RI, sTNF-RII and sIL-2R occurred when 19 patients in stage CDC I were compared to ten patients in stages II or III. The clearly elevated sTNF-RII levels in patients with horizontal and vertical HIV infection indicate the activation of the monocyte/macrophage system in both groups.
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PURPOSE: To evaluate the efficacy of video-intuboscopic assisted tracheal intubation in a difficult intubation setting. METHODS: In 50 pediatric patients (mean age 12.8 +/- 3.1 yr, range 6-16 yr) a grade 3 direct laryngoscopic view was simulated. Eight certified registered nurse anesthetists without experience in endoscopic intubation performed tracheal intubation on five or more patients using the video-optical intubation stylet. Time from insertion of the tube into the oral cavity until the tip had passed the vocal cords was recorded. Failed intubation was defined as intubation >60 sec, arterial oxygen saturation <92% or esophageal intubation. Subjective degree of difficulty was asked from the operators using a Likert-scale. RESULTS: Forty-six of the 50 patients were successfully intubated within 60 sec and without arterial oxygen desaturation. In four patients, video-assisted tracheal intubation failed due to prolonged intubation time. Intubation times ranged from 10-40 sec (median 15 sec). Mean intubation time in the first patient (24.5 +/- 17.3 sec) appeared longer than for the fifth patient (20.8 +/- 10.9 sec), but the difference was not statistically significant (P=0.87). Mean estimated degree of difficulty was 3.9 +/- 2.1. Subjective estimates of difficulty increased with intubation times (P=0.001). CONCLUSION: The video-optical intubation stylet can be considered a valuable aid for tracheal intubation in pediatric patients with a difficult airway.
This study was designed to examine the pharmacokinetics and toxicity of idarubicin (IDA) in rats. In two groups of rats IDA was infused either into the V. iugularis interna or into the A. carotis communis, respectively. The venous plasma concentration of IDA and its primary metabolite idarubicinol (IDOL) were measured up to 48 hours by high-performance liquid chromatography (HPLC) with fluorescence detection. The weights of the rats and the levels of haemoglobin, leukocytes, and thrombocytes were recorded. The plasma concentration-time data were analysed, assuming a biexponential disposition curve, both by the traditional (two-stage) method and by population pharmacokinetic modelling. The basic pharmacokinetic parameters clearance (CL = 27.0 ml min(-1)), mean disposition residence time (MDRT = 519.2 min), and volume of distribution at steady state (Vss = 12.51) were estimated for IDA. The mean residence time (MRT) of the generated IDOL was 2982.5 min. No significant differences between pre- and postpulmonal injection were found in the pharmacokinetics and pharmacodynamics of IDA. The mean survival time of 13.3 days is attributed to a severe myelosuppression.
UNLABELLED: A 2-month-old girl presented with fever, hepatosplenomegaly, pancytopenia, hypertriglyceridaemia and silvery-greyish hair, suggesting the diagnosis of Griscelli syndrome (partial albinism with immunodeficiency). This diagnosis was confirmed by the characteristic agglomeration of melanin in the hair shaft and accumulation of melanosomes in melanocytes of the skin. The patient was homozygous for polymorphic markers around the myosin-Va gene on chromosome 15q21, which co-localize to the Griscelli disease locus. Natural-killer cells were in the lower range. The stimulation of lymphocytes with antigen and mitogen was normal. The patient's accelerated phase, characterized by haemophagocytosis was treated with prednisolone, rabbit anti-thymocyte globulins, and intrathecal methotrexate. Remission was maintained with cyclosporin A until HLA-compatible peripheral blood stem cell transplantation from her mother. CONCLUSION: The silvery-greyish hair associated with fever, pancytopenia and hypertriglyceridaemia is the clue to early diagnosis of Griscelli syndrome and important to prevent death before stem cell transplantation.
Since the introduction of transcatheter interventional occlusion of atrial septal defects (ASDs) by King and coworkers, the device closure has become the standard treatment of selected atrial defects. Although it has become routine for standard clinical practice, increasing knowledge of intracardiac anatomy, modification of implantation techniques, and improvements in device designs are making this treatment modality increasingly applicable to a wider range of selected patients. This report summarizes the current trends in patient selection, focusing on the anatomical limits of applicability for ASD device closure, and discusses the future possibilities. Furthermore, typical complications are described with regard to the rare erosion of the atrial roof or the aortic root. Current practice is to oversize the device if the anterior rim toward the aorta tends to be diminutive, achieving a secure position of the device around the aortic root. This and the shape memory of the device may play a major role in this serious complication and should be reconsidered. Although most interventional occlusions of interatrial defects with a device have become clinically routine, some situations remain highly challenging.
Treatment of infants with posthemorrhagic hydrocephalus by diversion of CSF is frequently complicated by bacterial ventriculitis. We report the CSF values before and during bacterial ventriculitis of four very low birth weight infants with progressive posthemorrhagic ventricular dilatation. Extremely high CSF IL-6 concentrations of between 8,000 and 61,000 pg/ml were observed and compared with values reported in the literature. IL-6 seems to be a useful marker for bacterial ventriculitis in preterm infants. The role of IL-6 monitoring in the CSF of preterm infants with posthemorrhagic hydrocephalus for early diagnosis of bacterial ventriculitis prior to clinical manifestation should be clarified by further studies.
The Inventory of Functional Status-Fathers (IFS-F) was developed to measure the extent to which men continue or increase their usual household, social and community, childcare, personal care, occupational, and educational activities, and assume infant care responsibilities during their partners' pregnancies and the postpartum period. Content validity was established at 86%. Reliability testing used a sample of 125 expectant fathers and 57 new fathers. Internal consistency reliability using average correlations for the subscale item to subscale total scores ranged from .54 to .75. Subscale to total IFS-F score correlations ranged from .31 to .61. Initial construct validity testing was accomplished by examination of subscale correlations, which ranged from -.02 to .69. The IFS-F may be used to assess the functional status of men during the childbearing period for clinical and research purposes.
The purpose of this study was to evaluate the families of procreation of mothers with borderline personality disorder (BPD) on measures of family stability, family satisfaction, and family environment. Families of nine BPD mothers were compared with families of 14 mothers with other personality disorders using a semi-structured interview to evaluate family history, the Family Environment Scale (FES), and the Family Satisfaction Scale (FSS). Families of procreation of BPD mothers were more unstable than comparison group families. FES scores of BPD mothers were significantly lower than controls in cohesion and organization, but not in conflict. Instability and low family cohesion are common in families of BPD mothers, and may place their children at increased risk for development of psychopathology.