Biomedical subjects
C Jonas
Publications and source records attributed to C Jonas.
Activin A and activin receptors in thyroid cancer.
Proliferation is controlled by a network of mitogenic and growth inhibitory factors. Transforming growth factor-beta1 (TGF-beta1) and activin A are the most important growth inhibitors of benign follicular epithelial cells of the human thyroid. The effects of these substances on malignant primary thyrocytes are not known. We have examined the growth regulatory effects of activin A and TGF-beta1 in primary cultures derived from four papillary cancers, two follicular thyroid cancers, and three benign thyroid tissues. Malignant cells demonstrated resistance to activin and TGF-beta1 or reversal to a weak but significant mitogenic effect (p < 0.001). We also evaluated the activin receptor transcription pattern. Isoforms alk4-1, 4-2, and 4-3 were found in benign (n = 12) and malignant (n = 22) tissues. Two subtypes of type I and type II activin receptors were demonstrated. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a significant threefold downregulation of alk4-1 receptors in papillary (n = 25) and follicular (n = 18) thyroid cancers as compared to normal thyroids (n = 12) (p < 0.001). To our knowledge these are the first data to demonstrate reversal of activin and TGF-beta1 effects in thyroid malignancy and to demonstrate changes of the type Ib activin receptor expression in thyroid malignancy.
Group C meningococcal vaccine trial: safety, immunogenicity and parents' views of participation.
In 1995, the Oxford Vaccine Group evaluated the safety and immunogenicity of a Group C meningococcal conjugate vaccine in 182 infants using the UK vaccination schedule. During and after the study we sought the views of parents about the vaccine and about their participation in the trial. The vaccine was well tolerated and resulted in fewer local reactions than the routine vaccinations, with no increase in systemic reactions. Post-vaccination antibody levels increased progressively after each dose of conjugate vaccine. We concluded that this meningococcal C conjugate vaccine is safe and immunogenic. The research process and the views of parents provide important lessons for researchers undertaking trials on infants.
Activin A and activin receptors in the human thyroid: a link to the female predominance of goiter?
Activin A belongs to the TGF-beta family of growth factors involved in control of tissue formation by growth inhibition and to a family of hormones involved in human reproduction. Serum levels of dimeric activin A display a sexual dimorphism with significantly higher circulating hormone concentrations in men than in women after menopause. Since goiter is far more frequent in women than in men, we investigated the role of this sex-related growth factor in the human thyroid. Primary cultures were obtained from 3 patients with goiter, and 4 with recurrent goiter. Activin A significantly inhibited the proliferation of human thyroid follicular epithelial cells in vitro in concentrations between 0.5 and 50 ng/ml and was almost as potent as TGFbeta-1. Analysis in native tissues from 12 normal thyroids, 16 goiters, and 5 Graves thyroids demonstrated mRNA expression of the activin subunit betaA, TGFbeta-receptor type I and II, activin receptors type I receptors alk2 and alk4, and activin type II receptors actRII and actRIIb. Isoform analysis of the major functional type I activin receptor alk4 revealed the full-length transcript SKR2-1 and transcripts for the partially truncated proteins SKR2-2 and SKR2-3 in normal thyroids and goiters. Semi-quantitative RT-PCR revealed a significant 2.5-fold decrease of mRNA for alk4-1 type I activin receptors in goiter as compared to normal thyroid (p < 0.05), whereas expression of the type II receptor actRII was unchanged. These data identify a novel growth inhibitory pathway by activin in the human thyroid. Down-regulation of activin receptor type lb in goiter hints towards end-organ changes which could contribute to deficient growth inhibition. These data provide a mechanistic model how the sexually dimorphic hormone activin A may protect males from goitrogenesis.
Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy.
PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. PATIENTS AND METHODS: Forty patients with low-grade or follicular B-cell non-Hodgkin's lymphoma received six infusions of Rituxan (375 mg/m2 per dose) in combination with six doses of CHOP chemotherapy. RESULTS: The overall response rate was 95% (38 of 40 patients). Twenty-two patients experienced a complete response (55%), 16 patients had a partial response (40%), and two patients, who received no treatment, were classified as nonresponders. Medians for duration of response and time to progression had not been reached after a median observation time of 29 + months. Twenty-eight of 38 assessable patients (74%) continued in remission during this median follow-up period. The most frequent adverse events attributable to CHOP were alopecia (38 patients), neutropenia (31 patients), and fever (23 patients). The most frequent events attributed to Rituxan were fever and chills, observed primarily with the first infusion. No quantifiable immune response to the chimeric antibody was detected. In a subset of 18 patients, the bcl-2 [t(14;18)] translocation was positive in eight patients; seven of these patients had complete remissions and converted to polymerase chain reaction (PCR) negativity by completion of therapy. CONCLUSION: This is the first report demonstrating the safety and efficacy of Rituxan anti-CD20 chimeric antibody in combination with standard-dose systemic chemotherapy in the treatment of indolent B-cell lymphoma. The clinical responses suggest an additive therapeutic benefit for the combination with no significant added toxicity. The conversion of bcl-2 from positive to negative by PCR in blood and/or marrow suggests possible clearing of minimal residual disease not previously demonstrated by CHOP chemotherapy alone.
Eradication of Helicobacter pylori: why does it fail?
Currently, the first therapeutic attempt to eradicate Helicobacter pylori fails in one case out of six in intention to treat analysis. The main causes of failure are bad compliance, partly because of side effects that are severe in 1 to 4% of cases, absence of local validation of the treatment scheme, since some differences do exist between regions and countries, primary and secondary resistance of the strain (stable for Imidazole-derivates, but increasing for Macrolides), and, to a lesser extent, smoking and pre-treatment with proton pump inhibitors. Moreover, in routine medicine, inappropriate treatment cocktails are still prescribed, even by gastroenterologists. Obviously, there is a need for careful medical education and information both as far as concerns doctors and patients, for well-designed prescription, based on local experience and the precise previous history of every patient, as well as for continuous monitoring of the bacterial resistance to antibiotics. Culture of the strain is recommended after eradication failure with the classic one-week triple therapy, but if reliable culture and resistance testing are not available, the quadruple therapy as a second-line treatment is, so far, the best choice.
Radioimmunotherapy: special delivery.
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Rituxan: the new kid on the block.
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[How to eradicate Helicobacter pylori in 1995? Critical review of available treatments].
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Strategies for Helicobacter pylori eradication in 1995: a review of international and Belgian experience.
After a decade of research, Helicobacter pylori eradication is still a problem because of the steady increase of bacterial resistance (imidazole, macrolides), pH-dependent efficiency of antibiotics, poor compliance of patients and frequent side effects of the therapies. After the failure of various monotherapies and the unefficiency of Amoxicillin-Imidazole combination for Imidazole-resistant strains, the two weeks ¿Oral Triple Therapy' with a 85% mean eradication rate, was abandoned because of a mean 35% side effects rate. The current goal is to obtain 90% eradication rate and the excellent results of german studies with a 2 weeks regimen combining a Proton Pump Inhibitor (PPI) with Amoxicillin have not been confirmed elsewhere in Europe. PPI plus Clarithromycin (two weeks) gave a mean 72% eradication rate on an ITT basis. The short, low-dose combination PPI-Clarithromycin-Imidazole for one week proposed by Bazzoli is very efficient in a population where Imidazole resistant strains are rare. The recent result of one week with (Omeprazole 20-Clarithromycin 250-Tinidazole 500) BID or (Omeprazole 20-Clarithromycin 500-Amoxi 1000) BID reached a 95% eradication rate but these very promising results are not confirmed in Belgium in an on-going study including 147 patients.
[Role of psychiatry in the preoperative phase of facial reconstructive surgery].
Nowadays, the place of psychiatrist is currently admitted in facial plastic surgery, but is still discussed in reconstructive surgery. This page will stress the importance of a cooperation between surgeon and psychiatrist, preoperatively in orthognathic surgery. After a brief review of literature, we will try to precise when psychiatrist's advice would help, preoperatively, maxillofacial surgeon. On the other end, we will see that psychiatrist having in charge patients with major facial deformity can head them to undergo a reparatrice surgery. A clinical case will end this paper.
[Depression and suicide. The responsibility of the nursing staff].
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Omeprazole-based antimicrobial therapies: results in 198 Helicobacter pylori-positive patients.
AIM: To compare the efficacies of omeprazole-based antimicrobial therapies in Helicobacter pylori-positive patients. PATIENTS AND METHODS: We report the results of seven therapeutic trials combining omeprazole, clarithromycin, amoxycillin, colloidal bismuth subcitrate and tinidazole in 198 patients (peptic ulcer disease/non-ulcerative dyspepsia, 137/61) to eradicate H. pylori infection. The diagnosis of infection was performed by Sydney system biopsies, compliance was checked after a pill count at the end of the treatment and eradication was assessed at least 4 weeks after the end of the treatment either by the Sydney system for peptic ulcer disease or the urease breath test for non-ulcerative dyspepsia. RESULTS: When results were analysed on a protocol basis, the only significant difference in eradication (P = 0.006) was found between the total population of patients treated with amoxycillin-based combinations (27 eradications out of 48 patients) and those given a treatment that included clarithromycin (84 eradications out of 108). Forty-two patients (21%) dropped out either because of side effects (10 among patients taking clarithromycin and two taking amoxycillin) or because they were lost to follow-up (27 patients). Out of 64 patients with active ulcers, 43 (67%) were both H. pylori-negative and ulcer-free 4-8 weeks after the end of therapy, 12 out of 64 (19%) were ulcer-free but remained H. pylori-positive and nine out of 64 (14%) were H. pylori-positive and had active ulceration.
Influence of some bacterial and host factors on colonization and invasiveness of Escherichia coli K1 in neonatal rats.
Of 209 healthy infants examined, 44 (21.1%) carried Escherichia coli K1 in their feces. Of these 44 isolates, 36 (81.8%) were attributed to 10 different known clonal groups of E. coli K1 and 4 isolates represented unknown types. The influence of mannose-resistant (MR) adhesins, aerobactin production, and resistance to serum on colonization and invasiveness of E. coli K1 in orally infected inbred LEW baby rats was investigated. Strains expressing MR adhesins had significantly higher colonization and invasion rates than non-MR strains did. Mixed-infection experiments of LEW rats revealed interactions between different types of E. coli K1 strains affecting colonization and invasion rats. P-fimbriated strains appeared to have a selective advantage for colonization. The bacteremic potentials of different E. coli K1 strains could not be associated with their resistance to sera from LEW rats free of members of the family Enterobacteriaceae. No differences in virulence between fecal E. coli K1 isolates and clinical isolates from diseased humans were found. An influence of the major histocompatibility complex on host susceptibility to invasive E. coli K1 was indicated by comparing the parental LEW rat strain with different congenic LEW strains (RT1).
Biomedical research on incapacitated people according to French law.
In France, a law concerning biomedical research came into operation on 20 December 1988. This law is called loi Huriet after the senator who chaired the investigation committee. This law provides rules to be applied when research is conducted on incapacitated people. Different rules apply depending on whether the person concerned is an adult or not and whether he or she will benefit directly from the research. This law, and the law of 3 January 1968 concerning adult incapacitated persons, are discussed and their deficiencies are highlighted. Recommendations for improvements are made by the authors.
Offspring of diabetic mothers. Problems of morbidity.
In the past decade, malformation rates and life-threatening neonatal disorders of infants of diabetic mothers have been lowered to a marked degree. However, the remaining neonatal morbidity (metabolic and functional abnormalities and macrosomia) is still rather high. The meaning of these signs and symptoms for the further somatic development is unclear. A study comprising 443 neonatal infants of diabetic mothers was performed in order to quantify the morbidity. In 340 of the mothers, insulin treatment during pregnancy was based on HbA1c and blood glucose values; in the remaining 103 women, it was additionally controlled by measurement of insulin concentration in the amniotic fluid. A new classification of fetopathy at four different stages was established as a basis for further follow-up. In preparation of the latter, a pilot study including 160 infants in their fourth year of life was conducted to test the hypothesis that the further somatic growth is related to neonatal findings. The results demonstrate that the neonatal morbidity profile has changed with therapy. Metabolic control based additionally on insulin concentration in the amniotic fluid has resulted (1) in less infants with macrosomia and/or with striking phenotype but (2) also in a increase of small-for-gestational-age infants and of the frequency of hypoglycaemia. Only purely macrosomatic infants showed a tendency towards obesity and length acceleration in their fourth year of life.
Streptobacillus moniliformis isolated from otitis media of conventionally kept laboratory rats.
Streptobacillus moniliformis (Sm) was isolated from the middle ear of two inbred albino rats (strain CAP/Kuv) suffering from murine respiratory mycoplasmosis and purulent bilateral otitis media. The animals were kept under conventional conditions and used for immunological studies. The biochemical pattern of the isolate was identical with that of four other Sm strains of different origin but differed in its ability to lyse erythrocytes in sheep blood agar. This is the first Sm strain with hemolysis described. Pathogenicity of the strain was demonstrated in C57BL/6Han mice known to be susceptible to streptobacillosis. Three of five mice inoculated orally developed characteristic signs of a septic lymphadenitis. In the homologous system and with Sm strain ATCC 49567 as antigen, all five sera showed positive titers in the indirect immunofluorescence assay. Possible improvements in the diagnosis and the role of this "forgotten pathogen" in laboratory animal medicine are discussed.
Readers question the value of the MMSE.
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