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Biomedical subjects

C Roth

Publications and source records attributed to C Roth.

At least 91 records · Page 5Linked to original sources

Autoimmune thyreoiditis in childhood--epidemiology, clinical and laboratory findings in 61 patients.

Autoimmune thyroiditis (AT) is the most common cause of nonendemic goiter and acquired hypothyroidism in children and adolescents. In 61 patients AT was diagnosed following clinical, ultrasonographic, biochemical and cytological examinations. Girls were more often affected than boys, the female/male ratio in our patients was 9:1. Clinically the vast majority of patients had a goiter. Approximately half of the patients were euthyroid (n = 29). In the other patients hyperthyrotropinaemia (n = 16), hypothyroidism (n = 9) and hyperthyroidism (n = 7) were evident. Thyroid microsomal and peroxidase antibodies were elevated in most of the patients, while thyroglobin antibodies were less frequently elevated. As AT without detectable thyroid antibodies can occur, a fine-needle aspiration cytology of the thyroid is important in nontypical cases. This type of cytologic examination should also be considered in patients with euthyroid nonendemic goiter, thyroid nodules and hyperthyroid goiter.

Adolescent↗

Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: clinical, laboratory and genetic findings.

X-linked adrenoleucodystrophy (ALD) has been shown to be one of the most frequent causes of Addison's disease in men. It is characterized by an impaired peroxisomal beta-oxidation of very long chain fatty acids and is associated with mutations of the ALD gene resulting in a defective peroxisomal membrane transport protein. There is a striking variability of endocrinological and neurological symptoms in patients with ALD, with no clearly evident correlation between mutations of the ALD gene and the different neurological phenotypes. No data on endocrinological symptoms and the ALD genotype have been published so far. We report endocrinological, clinical, laboratory and molecular genetic data from 55 patients with ALD from 34 families. Endocrinological symptoms of adrenal insufficiency were observed in 33 patients, 20 of whom showed additional neurological symptoms of cerebral ALD or adrenomyeloneuropathy. Isolated neurological symptoms were seen in 12 patients; in nine patients there were neither endocrinological nor neurological symptoms. Mutations of the ALD gene (n = 28) were detected in 50 patients (including nine sets of brothers) from 32 families. No correlation was found between the ALD gene mutation and endocrinological dysfunction. However, we found that all sets of brothers were concordant for the endocrinological phenotype (cortisol synthesis was reduced in two sets and normal in seven sets), whereas four sets showed a discordant neurological phenotype. As yet unknown hereditary factors other than mutations within the ALD gene may interfere with the endocrinological phenotype more strongly than with the neurological phenotype of ALD.

Addison Disease↗

Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism.

Interleukin-10 (IL-10) is a recently described pleiotropic cytokine secreted mainly by type 2 helper T cells. Previous studies have shown that IL-10 suppresses cytokine expression by natural killer (NK) and type 1 T cells, thus down-regulating cell-mediated immunity and stimulating humoral responses. We here report that injected IL-10 protein is an efficient inhibitor of tumor metastasis in experimental (B16-F10) and spontaneous (M27 and Lox human melanoma) metastasis models in vivo at doses that do not have toxic effects on normal or cancer cells. Histological characterization after IL-10 treatment confirmed the absence of CD8+ and CD4+ T cells and macrophages at the sites of tumor growth, but abundant NK cells were localized at these sites. This unexpected finding was confirmed by showing that IL-10 inhibits most B16-F10 and Lox metastases in mice deficient in T or B cells (SCID and nu/nu mice), but not in those deficient in NK cells (beige mice or NK cell-depleted mice). However, IL-10 downregulation of pro-inflammatory cytokine production and/or recruitment of additional effector cells may also be involved in the anti-tumor effect at higher local concentrations of IL-10, since transfected B16 tumor cells expressing high amounts of IL-10 were rejected by normal, nu/nu, or SCID mice at the primary tumor stage, and there was still a 33% inhibition of tumor metastasis in beige mice.

Animals↗

Extracorporeal circulation, hemocompatibility, and biomaterials.

BACKGROUND: Performance of a majority of cardiac surgical procedures requires the use of extracorporeal circulation. Contact of the patients' blood with the nonendothelial surface of the cardiopulmonary bypass circuit is responsible for several, potentially harmful systemic reactions. METHODS: The patients' response to extracorporeal circulation is reviewed briefly. The interactions between patient and circuit are discussed not only as they relate to blood-material contact, but also from a mechanical and rheologic standpoint. The theoretic benefits of the newer, more hemocompatible materials are presented, along with a review of published clinical experience with heparinized cardiopulmonary bypass circuits. RESULTS: The response to extracorporeal circulation extends far beyond a simple derangement of hemostasis. This inflammatory response is strongly influenced by the rheologic design of the circuit and by the physical and chemical properties of the surface. Heparinized circuits decrease inflammation, but the clinical benefits of this reduction remain unclear, except for extended cardiopulmonary support. The safe use of these circuits requires full heparinization and does not reduce allogeneic transfusions. CONCLUSIONS: Clinicians are still in the search of the ideal material and the ideal extracorporeal circuit design. Newer, heparinized materials offer real but limited clinical benefits.

Biocompatible Materials↗

[Blood transfusion in surgery: can it still be reduced by human recombinant erythropoietin?].

New agents such as recombinant human erythropoietin (rHu EPO) modify conventional transfusionnal strategies. For accurate indications, such as, anaemia associated with chronic renal failure, cancer or cardiac disease, the preoperative prescription of rHu EPO may reduce transfusion requirements. rHu EPO may also be associated with pre-deposit transfusion in patients with anaemia before blood donation, when the transfusion needs are high, or the period for blood pre-deposit donation shortened. Postoperatively rHu EPO is only efficient if it is administered for a prolonged period; this condition limits its indications and value because of its high cost.

Aprotinin↗

Inhalation of 5-aminolevulinic acid: a new technique for fluorescence detection of early stage lung cancer.

Topical application of 5-aminolevulinic acid (5-ALA), with subsequent synthesis of protoporphyrin IX (PPIX), is a novel outstanding procedure for photodynamic treatment. So far, clinical experience has been reported with creams containing 5-ALA for the therapy of skin cancer, oral application for the treatment of gastrointestinal disease and intravesical instillation of 5-ALA solutions for fluorescence detection of superficial bladder cancer. Inhalation of 5-ALA for the staining of bronchial malignancies is a preferred method in clinical pulmonology. Since no adverse reaction was observed in lung function in a canine following inhalation of 5-ALA in increasing concentrations, clinical applications were performed. Seven patients with positive or suspicious sputum cytology, but negative white light bronchoscopy, received 5-10 wt.% 5-ALA in NaCl solution by means of a medical nebulizer. No side effects were observed during and after 5-ALA inhalation. After a period of 3 h, patients underwent fluorescence bronchoscopy using violet light for fluorescence excitation and an optical multichannel analyzer for fluorescence detection in situ. The results showed fluorescence spectra which could be related to PPIX induced by 5-ALA in the bronchial mucosa. The fluorescence intensity was sufficiently high for video imaging using a target integrating color CCD camera adapted to the flexible bronchoscope. Carcinoma in situ, as well as dysplasias, showed a clear positive fluorescence. A correlation of fluorescence contrast with histology on 30 biopsies revealed a high sensitivity, but a specificity below 50%. Improvements in light and drug dosimetry will form the basis for further clinical trials.

Administration, Inhalation↗

Late-afternoon ethanol intake affects nocturnal sleep and the sleep EEG in middle-aged men.

The effect of a moderate dose of ethanol (0.55 g/kg of body weight), administered 6 hours before scheduled bedtime, on performance, nocturnal sleep, and the sleep electroencephalogram (EEG) was investigated in 10 healthy, middle-aged men (mean age: 61.6 +/- 0.9 years). By the beginning of the sleep episode, breath-ethanol concentrations had declined to zero in all subjects. Compared with the control condition (mineral water), sleep was perceived as more superficial. Sleep efficiency, total sleep time, stage 1, and rapid eye movement (REM) sleep were reduced. In the second half of the sleep episode, wakefulness exhibited a twofold increase. EEG power density in low delta frequencies was enhanced in non-REM sleep (1.25-2.5 Hz) and REM sleep (1.25-1.5 Hz). In slow wave sleep (i.e., stages 3 + 4), power density was increased not only in the low-frequency range (1.25-1.5, 2.25-4.0, 4.75-5.0 Hz) but also within the alpha (8.25-9.0 Hz) and sigma (12.25-13.0 Hz) band. The data demonstrate that late-afternoon ethanol intake in middle-aged men disrupts sleep consolidation, affects the sleep stage distribution, and alters the sleep EEG.

Caffeine↗

Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by intratumoral administration of histoincompatible cells expressing human interleukin-2.

The production of human interleukin-2 (hIL-2) local to the tumor site by engineered histoincompatible cells has been shown in various murine models to promote a strong immune response leading to tumor growth inhibition or rejection. To assess whether this strategy would be similarly applicable for treatment of primary neoplastic cells, two naturally occurring tumors were used as preclinical models; the highly metastatic melanoma of the dog and the low metastatic fibrosarcoma of the cat. We demonstrate that both cats and dogs when treated by tumor surgery, radiotherapy and repeated local injections of xenogeneic Vero cells secreting high levels of hIL-2 relapse less frequently and survive longer than control animals treated by surgery and radiotherapy alone. Local secretion of hIL-2 by the xenogeneic cells is shown to be necessary for the induction of an optimal antitumor effect. Moreover, the safety of the procedure was demonstrated in both animal models and through extensive toxicological analysis performed in rats. These results confirm for the first time to our knowledge the safety and therapeutic potential of a gene transfer strategy in animals with spontaneous metastatic and nonmetastatic tumors.

Animals↗

Melatonin effect on daytime sleep in men: suppression of EEG low frequency activity and enhancement of spindle frequency activity.

The effect of melatonin (5 mg, p.o.) on electroencephalographic (EEG) activity during sleep was investigated in eight men in a placebo-controlled cross-over design. Melatonin was administered immediately prior to a 4-h daytime sleep episode (13-17 h) after a partial sleep deprivation. The non-REM sleep stages and REM sleep duration were not significantly affected. Melatonin enhanced EEG power density in non-REM sleep in the 13.75-14.0 Hz bin (i.e., within the frequency range of sleep spindles), and reduced activity in the 15.25-16.5 Hz band. In the first 2 h spectral values within the 2.25-5.0 Hz range were reduced. These changes in the EEG are to some extent similar to those induced by benzodiazepine hypnotics and to the contribution of the endogenous circadian pacemaker to the spectral composition of the sleep EEG when sleep occurs at night.

Adult↗

PCR-based analysis of the murine immunoglobulin heavy-chain repertoire.

The immunoglobulin heavy-chain repertoire has been mainly analysed by studying the proportion of genes belonging to each of the 14 described families, in terms of the expressed immunoglobulin molecules. Although the proportion of each variable gene family is kept stable throughout adult life and in different mice of the same strain, little information is available on the clonal representation in the repertoire of activated B cells. We describe here a new method that permits an approach to this question by separating the products of a polymerase chain reaction covering the VH-D-JH junction of the immunoglobulin heavy chain gene in a sequencing gel, thereby allowing discrimination of different rearrangements (according to their length) using a given JH and one of the member of a given VH family. Using this method, we show that it is possible to obtain a precise overview of the repertoire of activated B cells, at the mRNA level, as well as the potential repertoire, from a study of the DNA. We also show that this approach permits the detection of an induced immune B cell response and studies of emerging dominant specific B cell clones.

Animals↗

Characterization and detection of plant trypanosomatids by sequence analysis of the small subunit ribosomal RNA gene.

The complete sequences of the genomic small subunit ribosomal RNA gene from two Phytomonas isolates: one associated with palm pathologies (P. cocos FGuiana) and one found in lactiferous plants with no apparent pathology (P. Euphorbe Senegal), were analyzed. Partial sequences from a number of other Phytomonas isolates were also determined. The sequences obtained were used to determine the phylogenetic relationships between Phytomonas and other trypanosomatids as well as within the genus Phytomonas. The analysis showed that the intraphloemic isolates associated with pathologies in palm trees formed a homogeneous group that diverged from the more heterogeneous group of non-pathogenic isolates found in latex plant. Sequence comparisons of the full and partial SSU rRNA gene, identified sequences which are specific to the genus Phytomonas and an EcoRI restriction nuclease site which specifically identifies the Phytomonas isolates associated with diseases in palm trees.

Animals↗