Increased hexosaminidase activity in antipsychotic-induced extrapyramidal side effects: possible association with higher occurrence in bipolar disorder patients.

Dystonic movements and Parkinsonism are frequently seen in gangliosidoses and these conditions have been reported to modify dopaminergic plasticity. We investigated whether the activity of hexosaminidase, a type-two ganglioside (GM2) degrading enzyme, correlates with drug-induced extrapyramidal system (EPS) side effects in psychiatric patients. We compared hexosaminidase activity in the lymphocytes of 29 EPS-positive patients, 13 EPS-negative patients, and 30 healthy volunteers. The activities of A and B isoforms of hexosaminidase were higher in EPS-positive patients than EPS-negative patients and healthy controls. Multivariate analysis suggested an interaction with increased B isoform activity and EPS side effects in female bipolar disorder patients. Higher levels of hexosaminidase enzyme activity may explain the frequent occurrence of antipsychotic-induced extrapyramidal side effects in mood disorder patients.

Metabolic syndrome in Turkish children and adolescents.

The aim of this study was to determine the prevalence and phenotype of metabolic syndrome in Turkish children and adolescents. We adapted the National Cholesterol Education Program Adult Treatment Panel III criteria of metabolic syndrome to children and adolescents. Using the international cutoff points and percentiles, we determined 10- to 17-year-old Turkish children and adolescents with high blood pressure, high triglyceride (TG), low high-density lipoprotein cholesterol (HDL-C), fasting glucose of 100 mg/dL or greater, and elevated body mass index corresponding to overweight or obesity. We examined 1385 apparently healthy students between the ages of 10 to 17 years from Ankara, Turkey: 4.9% of the subjects were overweight or obese; 29.2% had either low HDL-C and/or high TG levels; and 15.7% had either systolic or diastolic blood pressure above the 95th age-, sex-, and height-specific percentile. Thirty students (2.2%) had metabolic syndrome by having 3 or more risk variables. Metabolic syndrome was nearly 10 times more common among overweight and obese students (21%), compared with lean students. Components of metabolic syndrome such as high blood pressure and high TG, and low HDL-C levels were common among Turkish children and adolescents. Strategies should focus on early detection and treatment of these risk variables in Turkish children.

Serum ribonuclease activity in the diagnosis of prostate cancer in men with serum prostate-specific antigen levels between 2.5 and 20 ng/mL.

OBJECTIVES: To evaluate the diagnostic value of serum ribonuclease activity for prostate cancer detection and to compare its performance with serum PSA. DESIGN AND METHODS: 111 subjects with serum PSA levels between 2.5 and 20 ng/mL underwent prostate biopsy. The diagnostic performance of serum ribonuclease activity, PSA, free PSA, complex PSA and PSA derivatives was studied in regard to discriminating prostate cancer from BPH. RESULTS: Of 111 patients, 27 (24.3%) were positive for prostate cancer. Median serum ribonuclease level in patients with prostate cancer was significantly higher than the non-cancer patients (21.3 U/mL vs. 6.6 U/mL, P < 0.001). Area under curve (AUC) values for ribonuclease activity level, PSA, f/tPSA and cPSA were 0.696, 0.514, 0.617 and 0.662, respectively. Of 27 patients with prostate cancer, radical prostatectomy was performed in 15. Of these 15 cases, four (26.7%) had clinical insignificant tumors; all with undetectable serum ribonuclease activity. When median values of various diagnostic parameters were compared in regard to predicting clinically significant and insignificant cancers, only serum ribonuclease activity was found to be significant. CONCLUSIONS: Although serum ribonuclease activity had no additional benefit beyond serum PSA in the diagnosis of patients with PSA levels between 2.5 and 20 ng/mL, it may be helpful to discriminate the clinically significant prostate cancers and thus select the proper treatment accordingly.

Body mass index and lipid levels in children from Ankara, Turkey versus Bogalusa, Louisiana.

BACKGROUND: Turkish Heart Study demonstrated that low high density lipoprotein cholesterol levels are prevalent among Turkish adults. METHODS: We compared body mass index and lipid levels of Turkish children (n = 1525, ages 10-17) with the bi-racial community of Bogalusa Heart Study. RESULTS: Turkish children have lower body mass index than American children (19.0 +/- 3 kg/m(2) for Turkish girls, 20.2 +/- 4 for White American girls, 20.9 +/- 5 for African American girls; and 18.9 +/- 3 kg/m(2) for Turkish boys, 20.2 +/- 4 for White American boys, 20.0 +/- 4 for African American boys, P < 0.01). Turkish children have higher triglyceride and lower high density lipoprotein cholesterol levels despite their lower body mass index. High density lipoprotein cholesterol levels (mmol/L) are 1.3 +/- 0.3 for Turkish girls and boys versus 1.4 +/- 0.5 for White American girls and boys, versus 1.6 +/- 0.5 and 1.7 +/- 0.5 for African American girls and boys, respectively (P < 0.01). Triglyceride levels (mmol/L) are 1.0 +/- 0.6 and 1.0 +/- 0.5 for Turkish girls and boys versus 0.9 +/- 0.5 and 0.8 +/- 0.5 for White American; and 0.7 +/- 0.3 for African American girls and boys, respectively (P < 0.01). CONCLUSIONS: Our observation of a lower HDL-C and a higher TG level in Turkish children (despite their lower BMI) is of interest and may indicate that unique characteristics in lipoprotein levels of Turkish adults start early in life.

Urinary glycosaminoglycans in the course of familial Mediterranean fever.

UNLABELLED: Familial Mediterranean fever (FMF) is characterised by recurrent fever and serositis. The most important complication of the disease is amyloidosis. Cheap and non-invasive methods would be important in predicting or establishing the early diagnosis of amyloidosis. For this purpose, we studied the role of urinary glycosaminoglycans (GAG). The study group included 123 FMF patients without an attack and 11 patients with FMF associated amyloidosis. Ten healthy children and ten patients with primary nephrotic syndrome served as controls. In patients with amyloidosis, urinary GAG were lower than in patients with FMF, patients with nephrotic syndrome and controls (median and range: 8.54 mg hexuronic acid/g creatinine (1.87-25.5), 5.8 (1.7-17.26), 23.12 (8.74-28.06) and 19.25 (14.2-26.9) respectively, P<0.01). There was a significant negative correlation between the duration of the disease and urinary GAG ( r= -043, P=0.002). In 49 FMF patients with a low GAG, urinary GAG increased significantly after an increase in the colchicine dose (median and range: 6.64 mg hexuronic acid/g creatinine (1.77-19.39) and 9.45 mg hexuronic acid/g creatinine (2.36-28.9), P<0.01). CONCLUSION: These results suggest that urinary glycosaminoglycan levels may be a predictor of amyloidosis in patients with familial Mediterranean fever. We also suggest that effective colchicine doses may be monitored by following urinary glycosaminoglycan excretion.

Biochemical and molecular characterization of mutant hexosaminidase A in a Turkish family.

BACKGROUND: Tay-Sachs disease is a form of monosialoganglioside triaose (GM2) gangliosidosis that results from the mutations in the alpha-subunit gene of hexosaminidase A. In the B1 variant, the active site of the alpha-subunit of the enzyme is thought to be affected. In the present study, a patient who had previously been diagnosed as a B1 variant is further analyzed. The patient's parents and brother were also analyzed. METHODS: Single-stranded conformational polymorphism (SSCP) and DNA sequencing analysis were conducted in all cases. In addition, hexosaminidase A (Hex A) was isolated from leukocyte homogenates of the patient's parents and brother using DE 52 ion-exchange chromatography, and thermostability analyses of the isolated enzymes were performed. RESULTS: Hexosaminidase A of the parents was found to be more thermostable than normal Hex A. DNA sequencing analysis revealed a 12-bp deletion mutation in exon 10 of the Hex A gene. The patient was a homozygote and the parents were heterozygotes for the mutation, which could also be observed at the DNA double strands by SSCP analysis. These deleted bases are located within the catalytic domain of the alpha-subunit. CONCLUSIONS: The 12-bp deletion mutation in exon 10 of Hex A is responsible for the increased thermostability of the enzyme. Considering this mutation has previously been found in a Turkish Tay-Sachs patient, the patient in the present study may have another mutation on the Hex B gene that causes decreased thermostability of the enzyme. Thermal inactivation assay may not be sufficient for a correct diagnosis in such unusual cases.

Histologic features of the liver in type Ia glycogen storage disease: comparative study between different age groups and consecutive biopsies.

In this report, the histologic criteria for the diagnosis of type Ia glycogen storage disease (GSD) in a wide age range were studied. Liver needle biopsies of 44 patients with type Ia GSD confirmed by enzyme analysis were re-evaluated and compared. Fatty change, nuclear hyperglycogenation (NH), and fibrosis were examined and graded. The second biopsies of 14 patients were also evaluated and compared with the first ones. The patients were grouped according to age: group I: <1 year (18 cases), group II: 1-5 years (19 cases), group III: >5 years (7 cases). A mosaic pattern was detected in all biopsies. The amount of fibrosis in group I was less than that in the other two groups. The fatty change in group I was more prominent. There was not much difference in the amount of NH between age groups. In comparing the two different biopsies of 14 patients, the amount of fibrosis was found to be increased in 7 cases. NH was also increased in a different group of 7 patients. These findings were both statistically significant. The amount of fatty change was minimal in most of the cases. Fibrosis is associated with types III, IV, VI, IX, and X GSD. Our results support previous studies stating that fibrosis may also be present and varies in extent in type I GSD. Fatty change as large lipid vacuoles and NH may not be seen in many cases of type I GSD. Therefore, histologic criteria for the diagnosis of GSD may not be specific, and enzyme analysis should be performed.