Familial Mediterranean fever (FMF) is a recessively inherited disorder predisposing to renal amyloidosis and associated with mutations in MEFV, a gene encoding a protein of unknown function. Differences in clinical expression have been attributed to MEFV-allelic heterogeneity, with the M694V/M694V genotype associated with a high prevalence of renal amyloidosis. However, the variable risk for patients with identical MEFV mutations to develop this severe complication, prevented by lifelong administration of colchicine, strongly suggests a role for other genetic and/or environmental factors. To overcome the well-known difficulties in the identification of modifying genetic factors, we investigated a relatively homogeneous population sample consisting of 137 Armenian patients with FMF from 127 independent families living in Armenia. We selected the SAA1, SAA2, and APOE genes-encoding serum amyloid proteins and apolipoprotein E, respectively-as well as the patients' sex, as candidate modifiers for renal amyloidosis. A stepwise logistic-regression analysis showed that the SAA1alpha/alpha genotype was associated with a sevenfold increased risk for renal amyloidosis, compared with other SAA1 genotypes (odds ratio [OR] 6. 9; 95% confidence interval [CI] 2.5-19.0). This association, which was present whatever the MEFV genotype, was extremely marked in patients homozygous for M694V (11/11). The risk for male patients of developing renal amyloidosis was fourfold higher than that for female patients (OR=4.0; 95% CI=1.5-10.8). This association, particularly marked in patients who were not homozygous for M694V (34.0% vs. 11.6%), was independent of SAA1-allelic variations. Polymorphisms in the SAA2 or APOE gene did not appear to influence susceptibility to renal amyloidosis. Overall, these data, which provide new insights into the pathophysiology of FMF, demonstrate that susceptibility to renal amyloidosis in this Mendelian disorder is influenced by at least two MEFV-independent factors of genetic origin-SAA1 and sex-that act independently of each other.

To study prospectively the risk factors and etiology of urolithiasis in all stone patients aged <15 years admitted from 1991 to 1999 to the Arabkir hospital in Yerevan. Stones were obtained by surgery (64%), extracorporeal shockwave lithotripsy (ESWL) (7%) or cystoscopic extraction (4%); 25% passed spontaneously. All were examined by infrared spectroscopy, and spot urines were analyzed chemically. 198 patients, 180 (68% males) with renal stones and 18 (83% males) with primary bladder stones, were studied. Calcium oxalate (CaOx) was the predominant constituent in 62% of the kidney stones, followed by struvite (17%), calcium phosphate (7%), uric acid (7%), ammonium acid urate (5%), and cystine (2%). Bladder stones contained CaOx in 72%, uric acid in 22% and ammonium acid urate in 6% of patients. Etiology was obviously metabolic in 5% and possibly metabolic in 26%. Twenty percent of stones were infectious, and 19% were endemic (9% bladder and 10% kidney stones); 4% were secondary to urinary stasis with malformation but no infection. Etiology in 26% remained unknown. Stone composition and metabolic etiology are similar to that in central Europe and North America. In contrast, infectious calculi and particularly endemic stones are still common, although becoming less so now. Urolithiasis in Armenia thus reflects the transition from a rural to an urban society.

Aim-To evaluate the presentation and course of acute postinfectious glomerulonephritis (APGN), which has increased dramatically in Armenia after serious deterioration in the living conditions. Study design-Observational study, based on case notes, of a large homogeneous group of patients hospitalised for APGN at one centre over a five year period (1992-6). Patients-474 patients aged <16 years with a diagnosis of APGN.Results-The annual number of patients increased tenfold from 19 (average 1992/3) to 196 in 1995. Sixty two per cent were in the age group 4-9 years and 65% were boys. Upper respiratory infections, scarlet fever, and skin infections preceded APGN in 51%, 23%, and 13%, respectively. All patients had haematuria (93% gross), 84% had oedema, and 72% had hypertension. C3 was initially decreased in 95% of the patients examined. Renal function was impaired (serum creatinine > 100 µmol/l) in 29%. Four patients with renal failure had crescentic glomerulonephritis at biopsy; of these, three required temporary haemodialysis. Main extrarenal complications were heart failure (10%) and convulsions (3%). One patient died and five (3%) did not recover completely. Conclusions-APGN in children is associated with considerable initial morbidity, and long term outcome is not uniformly benign. Outbreaks of APGN may occur anytime in countries such as Armenia that are suVering from a sudden decline in socioeconomic conditions.

Familial Mediterranean fever (FMF) is a recessively inherited disorder predisposing to renal amyloidosis and associated with mutations in MEFV, a gene encoding a protein of unknown function. Differences in clinical expression have been attributed to MEFV-allelic heterogeneity, with the M694V/M694V genotype associated with a high prevalence of renal amyloidosis. However, the variable risk for patients with identical MEFV mutations to develop this severe complication, prevented by lifelong administration of colchicine, strongly suggests a role for other genetic and/or environmental factors. To overcome the well-known difficulties in the identification of modifying genetic factors, we investigated a relatively homogeneous population sample consisting of 137 Armenian patients with FMF from 127 independent families living in Armenia. We selected the SAA1, SAA2, and APOE genes-encoding serum amyloid proteins and apolipoprotein E, respectively-as well as the patients' sex, as candidate modifiers for renal amyloidosis. A stepwise logistic-regression analysis showed that the SAA1alpha/alpha genotype was associated with a sevenfold increased risk for renal amyloidosis, compared with other SAA1 genotypes (odds ratio [OR] 6. 9; 95% confidence interval [CI] 2.5-19.0). This association, which was present whatever the MEFV genotype, was extremely marked in patients homozygous for M694V (11/11). The risk for male patients of developing renal amyloidosis was fourfold higher than that for female patients (OR=4.0; 95% CI=1.5-10.8). This association, particularly marked in patients who were not homozygous for M694V (34.0% vs. 11.6%), was independent of SAA1-allelic variations. Polymorphisms in the SAA2 or APOE gene did not appear to influence susceptibility to renal amyloidosis. Overall, these data, which provide new insights into the pathophysiology of FMF, demonstrate that susceptibility to renal amyloidosis in this Mendelian disorder is influenced by at least two MEFV-independent factors of genetic origin-SAA1 and sex-that act independently of each other.

The health of children and adolescents of Armenia has been affected by various socioeconomic, environmental, educational, and behavioral factors, demonstrating trends typical for both developed and developing countries. Key issues to be addressed by Armenian pediatricians are child mortality, malnutrition, and growth failure in the early years and overweight in later years. The case of Armenia illustrates how countries in transition are currently tackling both "old" problems (mortality and malnutrition) and "new" emerging morbidities (chronic diseases and adolescent health problems) based on social and health determinants, but the financing of the health system is far from satisfactory. Lessons of Armenia indicate the need for more cooperation between general practitioners and pediatricians at a primary care level. In addition, a better balance between inpatient and outpatient care could be achieved, which is not yet the case. Nevertheless, the overall performance of the Armenian child health care system can be considered satisfactory when bearing in mind the limitation of resources. Among the successful factors are those inherited from the Soviet period health system, including key institutions such as rural health posts and health centers, city polyclinics, and hospitals. These institutions mostly meet the needs of Armenian children and families today.