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FS Patients (f + patient)
Selected AbstractsImproved Cancer Pain Treatment Using Combined Fentanyl-TTS and TramadolPAIN PRACTICE, Issue 4 2007Franco Marinangeli MD ,,Abstract: The aim of the study was to facilitate dose escalation of strong opioids. In this randomized open-label study the influence of tramadol on dose adjustment of transdermal fentanyl in advanced cancer pain control was prospectively evaluated. Seventy patients affected by intractable cancer disease with visual analog scale (VAS) score >3 were enrolled. Thirty-five patients were treated conventionally with increasing transdermal fentanyl dosage as required (group F) and 35 patients received oral tramadol added to their transdermal fentanyl before each increment of the transdermal opioid dosage (group T). Pain control was equally satisfactory in the two groups. VAS scores at baseline (T: 4.36 ± 1.53; F: 4.51 ± 1.36; n.s.) and at the end of the study (T: 1.8 ± 1.6; F: 1.6 ± 1.5; n.s.) did not differ. However, in the tramadol group this level of pain control was achieved with much slower dose escalation of fentanyl. The mean application time of the fentanyl-Transdermal Therapeutic System patch for each dosage (25, 50, 75 ,g/hour) was significantly greater in patients receiving tramadol. No patient in group T escalated to the 100 ,g/hour patch, while in 12 patients of group F the 100 ,g/hour patch was applied after a 75 ,g/hour patch mean application period of 18.6 ± 4.7 days. The number of fentanyl-TTS dosage changes was significantly lower in group T (1.2 ± 0.4 vs. 2.3 ± 0.5; P < 0.05). The mean total duration of treatment in group T, was 37.1 ± 11.6 days. The amount of fentanyl used at study end was 56.6 ± 11.2 ,g/hour plus 141.1 ± 151.9 mg tramadol per day (median: 200 mg/day) in group T patients compared with 84.1 ± 12.2 ,g/hour in group F patients (P < 0.05). The combination of a strong opioid with a weak opioid to treat severe cancer pain allowed a more gradual increase of analgesic delivery than was possible using fentanyl-TTS alone, minimizing periods of under- and overdosing. In addition, it considerably slowed the pace of fentanyl dose escalation. In conclusion, this TTS fentanyl-tramadol analgesic protocol provides a useful alternative to the usual treatment of cancer pain with fentanyl-TTS alone, especially in case of quick progression of disease and pain.,, [source] An association between chronic infection with Chlamydia pneumoniae and lung cancer.APMIS, Issue 9 2001A prospective 2-year study This study assesses a possible relationship between chronic Chlamydia pneumoniae (Cpn) infection and lung cancer (LC). A total of 210 consecutive patients (136 M, 74 F) were diagnosed with LC during a 2-year period. Blood was obtained from 128 M and 70 F patients for Cpn serology. Repeat blood specimens were taken after 3 months. Throat specimens for Cpn DNA analysis by PCR were taken from 110/136 M and 63/74 F. Seventy-four cytobrush specimens were taken and also analyzed by polymerase chain reaction (PCR). Fifty (29 M, 21 F) bronchial biopsies and 8 (6 M, 2 F) tumors resected at surgery were analyzed for Cpn by immunohistochemistry (IHC). Males had significantly more often squamous-cell carcinoma (SCC) than females. Other types of LC were more equally distributed between males and females. The difference between males and females regarding smoking history was significant, and male LC patients had significantly higher levels of IgG and/or IgA antibodies than female LC patients. Male and female LC patients had significantly higher prevalences of high antibody titers than controls. A high prevalence of unusually high titers of specific Cpn antibodies was found in male LC patients. This could indicate that LC may be induced by chronic Cpn infection, since stable high titers of Cpn antibodies, especially IgA, are a hallmark of chronic infections. [source] Interindividual variability in the concentration,effect relationship of antilymphocyte globulins,a possible influence of Fc,RIIIa genetic polymorphismBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2008David Ternant WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT ,,There is interindividual variability in the antilymphocyte globulin (ALG) effect, but there is no pharmacokinetic,pharmacodynamic study of this subject. ,,In addition, a time dependence of the pharmacokinetics of some therapeutic antibodies has been described. ,,ALGs may partly act by antibody-dependent cellular cytotoxicity (ADCC), but their mechanism of action in humans is not known. WHAT THIS STUDY ADDS ,,Horse ALG pharmacokinetics can be described using a two-compartment model with time-dependent central volume of distribution. ,,After an initial concentration-independent lymphocyte depletion, the concentration,effect relationship can be described using a physiological indirect response model. ,,The genetic polymorphism of Fc,RIIIa at position 158 may influence the ALG concentration,effect relationship and these polyclonal antibodies may therefore act by ADCC. AIMS Polyclonal antilymphocyte globulins (ALGs) are currently used in transplantation, but the sources of interindividual variability of their effect are poorly understood. No pharmacokinetic,pharmacodynamic (PK,PD) study of ALG is available. Moreover, the genetic polymorphism of Fc,RIIIa, a receptor for the Fc portion of immunoglobulins involved in antibody-dependent cellular cytotoxicity (ADCC), may influence their concentration,effect relationship. METHODS Fourteen kidney transplant patients treated by horse ALG were included in a prospective, noncomparative study. A population two-compartment PK model including a time dependence of the central volume of distribution was developed. Total lymphocyte count was used as biomarker of effect. Concentration,effect data were described using a physiological indirect response model, combining concentration-dependent and -independent inhibitions of lymphocyte input into the circulation. In addition, six kidney transplant patients in whom ALG concentrations were not available were included retrospectively. All patients were genotyped for FCGR3A. RESULTS Both the PK and the PK,PD model described the data satisfactorily and showed high interindividual variability. Asymptotic T1/2 -, and T1/2 -,-values were 1.3 and 25 days, respectively. The concentration of ALG leading to a 50% inhibition of lymphocyte input (IC50) was lower in FCGR3A- V carriers than in FCGR3A- F/F patients (383 ± 199 vs. 593 ± 209 mg l,1, P = 0.008). CONCLUSIONS This is the first description of the ALG effect on lymphocyte count using PK,PD modelling. Our results show that part of the variability in their concentration,effect relationship may be explained by Fc,RIIIa genetic polymorphism and therefore that horse ALG may deplete lymphocytes by ADCC. [source] Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndromeMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2008Valérie Schumacher Abstract Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1,+,KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial,spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as ,testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1,+,KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line. Mol. Reprod. Dev. 75: 1484,1494, 2008. © 2008 Wiley-Liss, Inc. [source] Interleukin-10 is associated with resistance to febrile seizures: Genetic association and experimental animal studiesEPILEPSIA, Issue 4 2009Yoshito Ishizaki Summary Purpose:, Febrile seizures (FS) are the most common form of childhood convulsions. Many reports have shown that a proinflammatory cytokine, interleukin-1 (IL-1) ,, may have a facilitatory effect on the development of FS. We have previously shown that the IL1B -511C/T single nucleotide polymorphism (SNP) is associated with simple FS of sporadic occurrence. The balance between pro- and antiinflammatory cytokines influences the regulation of infections and could, therefore, play a role in the pathogenesis of FS. Here, to determine whether pro- and antiinflammatory cytokine genes are responsible for the susceptibility to FS, we have performed an association study on functional SNPs of cytokine genes in FS patients and controls. Methods:, The promoter SNPs of four inflammatory cytokine genes (IL6 -572C/G, IL8 -251A/T, IL10 -592A/C and TNFA -1037C/T) were examined in 249 patients with FS (186 simple and 63 complex FS) and 225 controls. Because the IL10 -592 SNP showed a positive association with FS, two additional SNPs (IL10 -1082A/G and -819T/C) were subjected to haplotype analysis. Furthermore, we examined the in vivo role of IL-10 in hyperthermia-induced seizures using immature animal models. Results:, The frequencies of the IL10 -592C allele and -1082A/-819C/-592C haplotype were significantly decreased in FS as compared with in controls (p = 0.014 and 0.013, respectively). The seizure threshold temperature in the IL-10,administered rats was significantly higher than that in the saline-treated control ones (p = 0.027). Conclusions:, The present study suggests that IL-10 is genetically associated with FS and, contrary to IL-1,, confers resistance to FS. [source] Increased Plasma Levels of Pro- and Anti-inflammatory Cytokines in Patients with Febrile SeizuresEPILEPSIA, Issue 8 2002Miia Virta Summary: ,Purpose: Pro- and antiinflammatory cytokines regulate the febrile response during infection. Febrile seizures (FSs) conversely are associated with rapid onset of high fever. Activation of the cytokine network has been shown in previous studies of FSs and cytokines. In this study, the association between cytokines and FSs was further investigated. Methods: Interleukin-1, (IL-1,), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), interleukin-10, and tumor necrosis factor-, plasma levels were measured with enzyme-linked immunosorbent assay in 55 children with FSs and in 20 age-matched febrile controls immediately on arrival at the hospital. Cerebrospinal fluid cytokine levels also were measured in 16 FS children. Results: The plasma IL-1RA/IL-1, ratio (mean, 2,133 vs. 119; median, 790 vs. 105; p < 0.0001) and plasma IL-6 (mean, 41.7 pg/ml vs. 16.1 pg/ml; median, 19.6 pg/ml vs. 10.5 pg/ml; p = 0.005) were significantly higher in FS patients compared with control children. Logistic regression analysis was used to find the most significant predisposing factors for FSs. In this analysis, the high plasma IL-1RA/IL-1, ratio was the most significant factor connected to FSs (OR, 41.5; 95% CI, 4.9,352.8), but high plasma IL-6 also was significantly associated with FSs (OR, 5.3; 95% CI, 1.4,20.3). Conclusions: Present results support the hypothesis that the cytokine network is activated and could have a role in the pathogenesis of FS. [source] Ganglioside mimicry and peripheral nerve diseaseMUSCLE AND NERVE, Issue 6 2007Nobuhiro Yuki MD Abstract Four criteria must be satisfied to conclude that a given microorganism causes Guillain,Barré (GBS) or Fisher (FS) syndrome associated with anti-ganglioside antibodies: (1) an epidemiological association between the infecting microbe and GBS or FS; (2) isolation in the acute progressive phase of illness of that microorganism from GBS or FS patients with associated anti-ganglioside IgG antibodies; (3) identification of a microbial ganglioside mimic; and (4) a GBS or FS with associated anti-ganglioside antibodies model produced by sensitization with the microbe itself or its component, as well as with ganglioside. Campylobacter jejuni is a definitive causative microorganism of acute motor axonal neuropathy and may cause FS and related conditions. Haemophilus influenzae and Mycoplasma pneumoniae are possible causative microorganisms of acute motor axonal neuropathy or FS. Acute and chronic inflammatory demyelinating polyneuropathies may be produced by mechanisms other than ganglioside mimicry. Muscle Nerve, 2007 [source] | ||||||||||