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Biomedical subjects

M Ramonet

Publications and source records attributed to M Ramonet.

11 recordsLinked to original sources

Contribution of anthropogenic and natural sources to atmospheric methane variability.

Methane is an important greenhouse gas, and its atmospheric concentration has nearly tripled since pre-industrial times. The growth rate of atmospheric methane is determined by the balance between surface emissions and photochemical destruction by the hydroxyl radical, the major atmospheric oxidant. Remarkably, this growth rate has decreased markedly since the early 1990s, and the level of methane has remained relatively constant since 1999, leading to a downward revision of its projected influence on global temperatures. Large fluctuations in the growth rate of atmospheric methane are also observed from one year to the next, but their causes remain uncertain. Here we quantify the processes that controlled variations in methane emissions between 1984 and 2003 using an inversion model of atmospheric transport and chemistry. Our results indicate that wetland emissions dominated the inter-annual variability of methane sources, whereas fire emissions played a smaller role, except during the 1997-1998 El Niño event. These top-down estimates of changes in wetland and fire emissions are in good agreement with independent estimates based on remote sensing information and biogeochemical models. On longer timescales, our results show that the decrease in atmospheric methane growth during the 1990s was caused by a decline in anthropogenic emissions. Since 1999, however, they indicate that anthropogenic emissions of methane have risen again. The effect of this increase on the growth rate of atmospheric methane has been masked by a coincident decrease in wetland emissions, but atmospheric methane levels may increase in the near future if wetland emissions return to their mean 1990s levels.

Atmosphere↗

Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition.

The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10(-24)) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA-DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II beta chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA-DRB1*0405 (RR = 10.4, Pc <.005) but not with HLA-DRB1*1301 or HLA-DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10(-4)). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P =.003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.

Adult↗

Short-term cyclosporine induces a remission of autoimmune hepatitis in children.

BACKGROUND/AIMS: The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone therapy, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process. METHODS: This is a pilot, multinational, multicenter, clinical trial involving children with autoimmune hepatitis. Thirty-two children were recruited, who according to international criteria were considered as having definite autoimmune hepatitis. Cyclosporine alone was administered for 6 months, followed by combined low doses of prednisone and azathioprine for 1 month, after which cyclosporine was discontinued. Biochemical remission of the disease was established by the follow-up of serum transaminase activity levels. Growth parameters and adverse effects of the treatment were recorded. RESULTS: Two patients were withdrawn from the study: one for non-compliance and the other for liver failure which did not improve with cyclosporine. Of the 30 remaining patients, 25 normalized alanine aminotransferase activity levels by 6 months and all the patients by 1 year of treatment. Z-scores for height showed a trend towards improvement during treatment. Adverse effects of cyclosporine were mild and disappeared during weaning off the medication. CONCLUSIONS: Cyclosporine induced the biochemical remission of the hepatic inflammatory/necrotic process in children with autoimmune hepatitis, with few and well-tolerated adverse effects.

Adolescent↗

Chronic active autoimmune hepatitis in children. Strong association with a particular HLA-DR6 (DRB1*1301) haplotype.

The association of HLA antigens and type I or "lupoid" CAH-C was investigated in a population of 52 Argentinian Caucasoid patients. When compared with a population of normal individuals of the same ethnic group (n = 197), a significant increase of HLA-DR6 was observed (68.6% in patients vs 17.3% in controls; RR = 12.3, chi 2 = 52.4, pc = 0.00001). DNA typing showed that the HLA-DRB1*1301 allele was present in 32 out of 33 HLA-DR6 patients (66.6% of all the C-CAH patients vs 10.5% in controls; RR = 16.2, chi 2 = 111.3, pc = 0.00001). Analysis of HLA-DQB1 alleles also showed a significant increase of DQB1*0603 (RR = 15.4, chi 2 = 106.5, pc = 0.00001), an allele found in strong linkage disequilibrium with DRB1*1301. The association of CAH-C with this particular HLA-DR6 haplotype has not been previously described for the adult onset CAH. This different HLA predisposition, together with the fact that extrahepatic autoimmune diseases occur frequently only in the adult form of the disease, suggest that the immunopathogenic mechanisms involved in the development of these diseases may be different.

Adolescent↗

[Liver ultrastructure in congenital atresia of the extrahepatic bile ducts].

Seven patients with diagnosis of biliary atresia (BA) and two patients with neonatal hepatitis were studied by electron microscopy. In all patients the diagnosis was done by clinical examinations, laboratory assays, histological studies by punch or surgical biopsies and or surgical examinations combined with intraoperatory cholangiography. The ultrastructural alterations found in both groups of patients were essentially similar to those described in other forms of cholestasis. In patients suffering from biliary atresia the main features found at hepatocytic livel were: Finely granular deposits of electron dense substance sometimes conforming lamellar structures; 2) Some increase and vesiculation of smooth endoplasmic reticulum membranes; 3) Reductions in number and length of sinusoidal microvilli; in some areas was also detected basal membrane and an increase in the amount of collagen fibers in the space of Disse; 4) Marked bile canaliculi dilatations with reduction of microvilli and thickening of the pericanalicular surrounding area, some canaliculi were constitued by several hepatocytes. Ductules were found in only 3 cases with the following alterations: 1) Intracytoplasmic electron dense deposits of granular material without limiting membranes; 2) A marked increase in the number of microfilaments mainly located in the apical portion of the cell or in the vicinity of the nuclei; 3) Inflammatory cells in the duct epithelium or in direct contact with the hepatocytes. The ultrastructural findings in the two cases of neonatal hepatitis (NH) resembled those described in the biliary atresia.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Ducts↗

Giardiasis. Functional, immunological and histological study of the small bowel. Therapeutic trial with a single dose of tinidazole.

Fourteen patients between the ages of 9 months and 5 years with chronic diarrhea and giardiasis were studied. Ten were eutrophic and 4 undernourished. The parasitological diagnosis was based on stool examination, a trophozoite search in duodenal aspiration, mucus adhered to mucosa and parasite identification in the intestinal biopsy material. Functional intestinal absorption studies, IgA determination in intestinal secretions and immunofluorescence studies were made. After the tests, tinidazole in suspension was administered at 60-70 mg/kg in one single oral dose. Patients were clinically re-evaluated and tests were done again after 30 days. The purpose of this paper was to evaluate the changes in the functional morphologic and immunologic studies and the therapeutic efficacy of the drug in a single dose. Nine patients had good clinical results, 2 fair and 3 were not evaluated due to celiac disease. All had negative results on the parasitological tests after treatment. There was no relationship between the number of parasites and the severity of symptoms. There was no significant difference between stool fat and d-xylose at the time of diagnosis and 30 days after the administration of tinidazole. The lactose tolerance test presented a significant difference (p less than 0.05) in the disaccharide absorption after treatment. The secretory IgA revealed significantly lower value (p less than 0.01) with respect to the normal values. The immunofluorescence showed productive IgA cells in all cases. The histologic changes were: mild enteropathy (grade I) in 6 patients; moderate (grade II) in 5; and severe (grade III-IV) in 3. Improvement of the mucosa was seen in 6 patients.

Administration, Oral↗

Circulating antibodies to cow's milk proteins in children with acute diarrhoea.

Circulating antibodies to cow's milk protein were investigated in 35 normally nourished infants aged 2 to 11 months. Nine were healthy (control group), and the remaining 26 were convalescents from acute diarrhoea. At the time of assay they were normally hidrated and being fed diluted cow's milk. The results showed elevated hemagglutinating antibody titers in the group of children with diarrhoea, statistically different to the control (p less than 0.001). The existence of an enhanced absorption of non degraded milk protein during the disease is assumed. This observation constitutes one more element in favour of the risk of exposing the digestive tract to antigenic loads in pathological situations as those considered.

Acute Disease↗