PubMed Health⌕ Search

Biomedical subjects

G Rostoker

Publications and source records attributed to G Rostoker.

At least 19 recordsLinked to original sources
PubMed2005

Smoking cessation guidelines: evidence-based recommendations of the French Health Products Safety Agency.

Tobacco use is the leading preventable cause of death in developed countries. Millions of smokers are willing to stop, but few of them are able to do so. Clinicians should only use approaches that have demonstrated their efficacy in helping patients to stop smoking. This article summarizes the evidence-based major findings and clinical recommendations for the treatment of tobacco dependence of the French Health Products Safety Agency (AFSSAPS). Clinicians should enquire about the smoking status of each patient and provide information about health consequence of smoking and effective treatments available. These treatments include counseling (mainly individual or social support and behavioral and cognitive therapy) and pharmacological treatment with either nicotine replacement therapy (NRT) or bupropion LP. Pharmacological treatments should be used only for proven nicotine dependence, as assessed by the Fagerstrom test for Nicotine Dependence. The choice of pharmacologic treatment depends of the patient's preference and history and of the presence of contra-indications. The clinician should start with a single agent, but these treatments may be used in combination. Smoking behavior is a chronic problem that requires long-term management and follow-up. Access to intensive treatment combining pharmacological treatment and extensive behavioral and cognitive therapy should be available for highly dependent patients.

Evidence-Based Medicine↗
PubMed2001

Increased intestinal intra-epithelial T lymphocytes in primary glomerulonephritis: a role of oral tolerance breakdown in the pathophysiology of human primary glomerulonephritides?

BACKGROUND: There is increasing evidence that some organ-specific and generalized autoimmune diseases in humans might be related to a breakdown of oral tolerance. We explored this hypothesis in human primary glomerulonephritides. We prospectively counted intraepithelial T lymphocytes in the duodenal mucosa (as a marker of rupture of oral tolerance), together with IgA1 and IgA2 mucosal plasma cells, in patients with primary glomerulonephritides. METHODS: We investigated eight adults with immune-complex glomerulopathy (membranous nephropathy+membranoproliferative glomerulonephritis), 16 adults with an idiopathic nephrotic syndrome, and 25 adults with IgA nephropathy. Patients with glomerulonephritides were compared to two control groups: group 1 consisted of nine healthy adults; group 2 comprised five adults with coeliac disease before dietary gluten withdrawal or during a clinical relapse related to gluten ingestion. (The latter disease is associated with increased numbers of intraepithelial T lymphocytes, and a breakdown of oral tolerance to gliadins is involved in the pathogenesis of coeliac disease). Duodenal fibroscopy was performed under neuroleptanalgesia. Four to six endoscopic biopsy specimens were taken from the second duodenum. Intraepithelial T lymphocytes were blindly counted on paraffin sections stained with haematein-eosin-saffron (HES), within the epithelium of a villus in a zone with at least 100 cells. Mucosal IgA1 and IgA2 plasma cells were blindly counted in a mucosal tissue unit by using specific mouse monoclonal antibodies directed against IgA1 and IgA2, with alkaline phosphatase anti-alkaline phosphatase (APAAP) revelation. As values were not normally distributed, we used non-parametric analysis of variance with the Kruskal-Wallis test, and compared median values by using the non-parametric Mann-Whitney test. RESULTS: Intraepithelial T lymphocytes were significantly more abundant in patients with primary glomerulonephritides and coeliac disease than in healthy controls (P < 0.0001 in the Kruskal-Wallis test): healthy controls, median 11 (range 4.65-16); immune complex glomerulopathy, 27.45*** (15-93); idiopathic nephrotic syndrome, 16.5** (9-26.5); IgA nephropathy, 26.10*** (11.3-47.5); coeliac disease, 55*** (20-80) (*P <0.05; **P <0.01; ***P < 0.005, Mann-Whitney test). No difference was found in the number of duodenal IgA1 and IgA2 plasma cells between controls and patients with primary glomerulonephritides. IgA1 and IgA2 plasma cells were increased in patients with coeliac disease. CONCLUSION: The significant increase in intestinal intraepithelial T lymphocytes in primary glomerulonephritides suggests a pathophysiological role of oral tolerance breakdown.

Antigen-Antibody Complex↗
PubMed2001

Schönlein-henoch purpura in children and adults: diagnosis, pathophysiology and management.

Schönlein-Henoch syndrome is a form of systemic small-vessel vasculitis, characterised by vascular and/or mesangial immunoglobulin A1 deposits. The main clinical manifestations are vascular purpura, predominating on the lower limbs, and articular, gastrointestinal and renal symptoms. Pulmonary, cardiac, genital and neurological symptoms have also be observed. The syndrome usually affects children, whereas it is rare in adults. The frequency of renal involvement varies between individual studies (from 20 to 100%). Renal manifestations are usually mild and transient, although chronic nephropathies may occur. Overall, an estimated 2% of children with Schönlein-Henoch purpura progress to renal failure and up to 20% of children with nephritis treated in specialised centres require haemodialysis. The renal prognosis appears to be worse in adults. Aetiological investigations are required, as a triggering factor is found in approximately half the patients (e.g. viral, bacterial and parasitic infections, drugs, toxins, systemic diseases and cancer). Dapsone has beneficial effects on cutaneous, gastrointestinal and articular manifestations in adults, especially those with chronic forms. Corticosteroids may be useful for refractory abdominal pain. Methylprednisolone pulse therapy, immunosuppressive drugs (e.g. cyclophosphamide and azathioprine), plasma exchange and polyclonal immunoglobulin therapy are beneficial in very rare life-threatening forms of the disease and in rare instances where renal function is compromised.

Adult↗
PubMed2000

Vascular hyperpermeability in nephrotic edema.

BACKGROUND/AIM: There is increasing evidence that hypoalbuminemia and the inability of the renal distal tubule to excrete salt are not the only factors responsible for nephrotic edema. We tested the possibility that vascular hyperpermeability also plays a role in the pathophysiology of nephrotic edema in human primary glomerulonephritis. METHODS: We investigated the capillary permeability by means of a standardized test using albumin labelled with technetium (99mTc-albumin) in 20 healthy adults and in 101 nephrotic adult patients comprising 60 patients with idiopathic nephrotic syndrome (INS; minimal-change nephropathy and segmental glomerulosclerosis), 32 with idiopathic membranous nephropathy (IMN) and 9 patients with idiopathic type I membranoproliferative glomerulonephritis (MPGN). The patients and healthy controls were also compared with a group of women (n = 25) with idiopathic cyclic edema, a disease in which an increase in capillary permeability plays a pivotal role. The capillary permeability measured by the Landis isotope test is normal in edematous patients with cardiac and renal impairment unrelated to glomerular disease, cirrhosis, hypothyroidism, lymphatic obstruction and diuretic abuse. As values were not normally distributed, nonparametric analysis of variance was used (Kruskal-Wallis test), and patient groups were compared with healthy controls and with women with idiopathic cyclic edema by means of the two-tailed nonparametric Mann-Whitney test. The effects of high-dose steroids and Ginkgo biloba extract (Tanakan); an agent able to improve capillary permeability) were analyzed by means of the two-tailed nonparametric Wilcoxon test. RESULTS: The capillary permeability was significantly increased (Mann-Whitney test) in each glomerular disease group compared with the healthy controls. 99mTc-albumin extravasation values (%; median and range in parentheses were the following: healthy controls 0 (0-8.4); idiopathic cyclic edema patients 11.5 (8-24), p < 0.001; INS 20 (0-50), p < 0.0001; IMN 12.5 (0-40), p < 0.001, and MPGN 10 (0-40), p < 0.05. An increase in capillary permeability exceeding the upper limit of control values (>8% of 99mTc-albumin extravasation) was observed in 88% of INS, in 53% of IMN and in 44% of MPGN patients. The increase in capillary permeability (%) was greater in idiopathic nephrotic patients than in idiopathic cyclic edema patients (p < 0. 005, Mann-Whitney test) and was markedly reduced in nephrotic patients receiving high-dose steroids (n = 8) [before 25 (8-40); after 0 (0-25), p < 0.005 (Wilcoxon's test)] and high doses of G. biloba extract (n = 16) [before 30 (8-50); after 2.5 (0-20, p < 0. 0005 (Wilcoxon's test)]. CONCLUSIONS: We conclude that capillary permeability is severely altered in most of the nephrotic patients with primary glomerulonephritis. These results strongly suggest that the capillary hyperpermeability plays a role in the pathophysiology of nephrotic edema in primary glomerular disease, especially in INS. We postulate that this widespread abnormality in capillary permeability is related to the release of vascular permeability factor and other cytokines by immune cells.

Adolescent↗
PubMed1998

Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis, and a potential target of immunoglobulin therapy?

Following recent experimental data suggesting an aggravating effect of circulating proinflammatory cytokines on the histological lesions of IgAN, we studied changes in serum proinflammatory cytokines and their soluble receptors and antagonists in patients treated with polyvalent immunoglobulins (15 with severe nephropathy who had indicators of poor prognosis: heavy proteinuria, hypertension, altered renal function and Lee's histological grade III or IV; and 14 with moderate forms of IgAN who had permanent albuminuria > 300 mg/day and < 2000 mg/day, Lee's histological grade II and a glomerular filtration rate > 70 ml/min) in comparison with healthy controls (n = 20) and patients with non-IgA nephritides (n = 50). These were measured by means of specific immunometric assays before and after 9 months of immunoglobulin therapy. Total tumour necrosis factor (TNF) serum and IL-6 levels were elevated in IgAN patients before therapy, relative to controls, and normalized after immunoglobulin therapy. Levels of soluble TNF receptor of type I (sR55) and type II (sR75) increased on immunoglobulin therapy. TNF index alpha-55,75 used to assess biologically available TNF-alpha (ratio of total TNF-alpha divided by levels of soluble TNF receptors sR55 and sR75) was elevated before therapy and was below healthy control values after 9 months of immunoglobulin administration. Levels of serum IL-1 receptor antagonist were low prior to immunoglobulin administration in patients with severe forms of IgAN, and normalized on therapy. Serum interferon-gamma was unmodified. The histological activity index correlated with serum total TNF-alpha, TNF index alpha-55,75 and serum IL-6 levels, whereas proteinuria correlated with serum total TNF-alpha and TNF index alpha-55,75 but not with serum IL-6. These data suggest that the overproduction of proinflammatory cytokine is unbalanced by their natural antagonists in IgAN and Henoch-Schönlein syndrome. This process may play a role in the progression of the disease and be one of the targets of immunoglobulin therapy.

Antigen-Antibody Complex↗
PubMed1997

Role of lipoprotein-bound NEFAs in enhancing the specific activity of plasma CETP in the nephrotic syndrome.

Plasma cholesteryl ester transfer protein (CETP) activity, evaluated by the transfer of radiolabeled cholesteryl esters from a tracer dose of tritiated HDL to the plasma apolipoprotein B-containing lipoproteins, was significantly higher in patients with untreated idiopathic nephrotic syndrome (n = 15) than in normolipidemic control subjects (n = 22) (81.5 +/- 8.4 versus 43.1 +/- 3.1 micrograms CE.mL-1.h-1, respectively; P < .001). The increased CETP activity in nephrotic plasma was explained by a significant rise in both the CETP mass concentration (3.2 +/- 0.2 versus 2.1 +/- 0.1 mg/L; P < .001), and the specific CETP activity, calculated as the ratio of CETP activity to CETP mass (25.3 +/- 1.7 versus 20.4 +/- 1.6 micrograms CE.mg-1.h-1; P < .05). Elevated CETP activity in nephrotic patients was shown to be associated with a significant decrease in the mean size of LDL (24.4 +/- 0.5 versus 26.3 +/- 0.5 nm; P < .0001) as well as in the relative abundance of HDL2a (29.6 +/- 1.6% versus 34.8 +/- 1.1%; P < .05). The nephrotic syndrome was characterized by a significant increase in the relative proportion of lipoprotein-bound nonesterified fatty acids (NEFAs) (35.4 +/- 7.7% versus 7.6 +/- 3.0% of total; P < .01), leading to a significant increase in the electronegative charge of LDL (-4.3 +/- 0.1 versus -3.9 +/- 0.1 mV; P < .05) and HDL (-11.5 +/- 0.1 versus -11.1 +/- 0.2 mV; P < .05). Compared with native, non-supplemented plasma, removal of lipoprotein-bound NEFAs by addition of fatty acid-poor albumin to total plasma from nephrotic patients or control subjects significantly decreased CETP activity and specific CETP activity. Specific CETP activity no longer differed between nephrotic and control groups after albumin supplementation (19.7 +/- 1.5 versus 17.7 +/- 1.5 micrograms CE.mg-1.h-1; NS). It is concluded that, in addition to elevated CETP mass concentration, lipoprotein-bound NEFAs, by increasing the negative electrostatic charge of nephrotic lipoproteins, can facilitate the CETP-mediated neutral-lipid transfer reaction in total plasma from nephrotic patients.

Adult↗
PubMed1997

Drug-induced linear IgA disease: target antigens are heterogeneous.

No information is available concerning the target antigen(s) in drug-induced linear IgA disease. The purpose of this study was to define better drug-induced linear IgA disease by studying its immunopathological, immunoultrastructural and immunochemical characteristics in three patients. In the first patient, IgA deposits were seen in the lamina lucida. In the second and the third patients, IgA deposits were seen on each side of the lamina densa. Immunoblotting of the first patient's serum showed that IgA reacted with a protein of 230 kDa similar to the bullous pemphigoid-associated antigen 1 (BPAG 1). The second patient's serum did not react with specific bands. In the third patient IgA antibodies reacted with a protein of 97 kDa on epidermal extracts. Our findings suggest that, as in idiopathic forms, the target antigen is not unique in drug-induced linear IgA disease. In some patients, drug-induced linear IgA disease may represent an IgA class response to the BPAG 1.

Adult↗
PubMed1996

Type I membranoproliferative glomerulonephritis and HCV infection.

Type I membrano-proliferative glomerulonephritis (MPGN) is secondary to chronic bacterial, parasitic, viral (HB) infections, to autoimmune disorders or primary or malignant haemopathies. MPGN are thought to be linked to the deposition of immune complexes preformed in the circulation or formed in situ in the glomeruli. A link between HCV and type I MPGN was reported for the first time in 1993. In some patients, the renal clinical pattern is the most obvious (nephrotic syndrome) whereas in others liver disease or cryoglobulinaemia prevail. A risk factor of HCV infection exists in 80% of cases. Renal biopsy and scanning electron microscopy usually substantiate cryoglobulinaemia. Circulating cryoglobulins are most often detected, usually of type II. CH50 is decreased in 90% of patients and rheumatoid factors have been found in two-thirds of patients. The cryoprecipitate contains viral RNA and anti-HCV antibodies. The viral RNA is nearly always found in the cryoprecipitate. Analysing the viral genotype does not elicit predominance of any particular type. Viral genome detection in renal biopsy specimens appears to be technically difficult. Type I MPGN secondary to HCV infection appear to be improved by interferon-alpha therapy but treatment suspension is immediately followed by the recurrence of viraemia and nephrotic syndrome. Serological tests to detect anti-HCV antibodies and viral RNA by PCR in type I MPGN, so far considered as 'primary', are scarce and produce conflicting results: there might be a link between those glomerulopathies and HCV infection in the USA and in Japan only, not in Europe.

Antibodies, Viral↗
PubMed1995

Further identification of human plasma glycoproteins interacting with the galactose-specific lectin Jacalin.

In this report we show that Jacalin binds the heme-binding protein hemopexin and the C4b-binding protein sgp120 in human plasma. The interaction of Jacalin with hemopexin confirms that a single O-linked oligosaccharide is sufficient to mediate binding of a protein to this lectin. Retention of sgp120 by immobilized Jacalin demonstrated that this protein was O-glycosylated and, therefore, clearly different from another C4b-binding protein, the complement protein C2 which is physicochemically similar but exclusively N-glycosylated. In addition, Jacalin was also shown to bind several proteolytic enzymes which remain to be identified.

Amino Acid Sequence↗
PubMed1995

Prevention of thrombotic complications of the nephrotic syndrome by the low-molecular-weight heparin enoxaparin.

The nephrotic syndrome (NS) carries one of the highest risks of thrombotic complications. Consequently, over the last 15 years, some nephrologists have treated patients risk (i.e. those with albuminemia < 20 g/l and membranous nephropathy) with anticoagulants: either subcutaneous heparin (Kakkar protocol) or antivitamin K. Low-molecular-weight heparin (LMWH) has a longer plasma half-life and better bioavailability than standard heparin and can thus be administered as a single daily injection. LMWH also carries a lower risk of hemorrhage. We prospectively studied the safety and efficacy of the LMWH Enoxaparin for preventive anticoagulation in NS. In a preliminary study, 10 adult nephrotic patients with biological markers of thrombosis risk (severe hypoalbuminemia and/or anomalies of the fibrinolytic pathway and/or deficiency in coagulation inhibitors) were given 40 mg (4,000 U) of Enoxaparin daily for at least 3 months; 3 patients were treated for 3 months, 1 for 6 months and 6 for 12 months. Patients were assessed for silent thrombosis, using renal vein Doppler ultrasonography, lower leg vein Doppler ultrasonography and lung ventilation-perfusion scintigraphy, before entry to the trial and subsequently at 3-month intervals. As LWMH caused no obvious side effects and no thrombosis was observed during the pilot study, we then placed 55 adult nephrotic patients free of thrombosis on the same treatment. Patients were seen according to the usual calendar required by their individual illnesses. At each examination, patients were assessed for clinical signs and symptoms of thrombosis and side effects; plasma D-dimer and urinary fibrin-fibrinogen degradation products were also measured at each visit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗