Leiden, G20210A mutations in prothrombin gene and antiphospholipid antibodies in systemic lupus erythematosus and antiphospholipid syndrome

AIM: To estimate incidence rate of Leiden mutation in factor V gene, prothrombin gene mutation responsible for replacement of G for A in position 20210 (G20210A) of its 3'-end noncoding part in patients with systemic lupus erytheamtosus (SLE) and antiphospholipid syndrome (APS) and their relationships with antiphospholipid antibodies (aPL): lupus anticoagulant (LA) and anticardiolipin antibodies (aCL). MATERIALS AND METHODS: The trial included 33 patients (2 males and 31 females) aged 20-62 years (mean age 32.7 +/- 9.8 years). 29 patients suffered from SLE, 17 of them had also APS (criteria by G. R. V Hudhes). 3 patients had primary APS, 1 female had hemorrhagic vasculitis. IgG and IgM-aCL were detected by enzyme immunoassay. In revealing mutation, DNA was used isolated from peripheral blood by standard methods based on polymerase chain reaction (PCR). Primary screening of Leiden mutation was made according to Bertina et al. with Mnl I restrictase. The mutation was confirmed by an original technique with allele-specific primers. G20210A mutation in the prothrombin gene was determined with restrictase Taq I after introduction of artificial restriction site in PCR product. The patients were divided into 2 groups. Group 1 incorporated 12 patients with SLE without APS. Group 2--21 patients with APS (17 with SLE + APS, 3 with primary APS and 1 with hemorrhagic vasculitis). RESULTS: Patients of group 1 had neither thrombotic complications nor Leiden mutation. Two patients of group 2 had heterozygous Leiden mutation. Both females were aPL-positive and had previously recurrent thrombophlebitis. One of them had also recurrent disorders of cerebral circulation. None of the examinees had any G20210A mutations in the prothrombin gene. CONCLUSION: Detection of genetic defects in APS provide arguments in the dispute about the necessity, duration and choice of anticoagulant therapy. If patients with APL syndrome appeared to have besides aPL also genetic defects in coagulation, this will enable identification of patients at high risk of thrombosis which need permanent administration of anticoagulants among which only low-molecular ones or glycosaminoglycanes are indicated. Mutation in gene of factor V is absolute contraindication to phenilin and quamarines.     

Combined therapy with amlodipin and lisinopril in arterial hypertension: efficacy of a low-dose combination

AIM: To assess antihypertensive efficacy of a low-dose combination of amlodipin with lisinopril in the treatment of patients with arterial hypertension (AH) of the second degree. MATERIAL AND METHODS: A total of 42 patients with the second degree of AH (16 males, 26 females, mean age 55-9 +/- 1.9 years) entered an open, comparative and controlled trial. They were divided into three groups by the treatment. Group 1 (n = 14) received amlodipin (normodipin, Gedeon Richter) monotherapy in a mean dose 8.9 +/- 0.6 mg/day, group 2 (n = 12) - lisinopril (diroton, Gedeon Richter) in a mean dose 17.5 +/- 1.4 mg/day, group 3 (n = 16) was given combined therapy with amlodipin+lisinopril in a dose 6.8 +/- 0.7 and 8.7 +/- 0.6 mg/day, respectively. The drugs were given for 12 weeks. The efficacy of the treatment was assessed by the results of 24-h monitoring of blood pressure, echocardiography, endothelium-related vasodilatation of the brachial artery (ERVD), dopplerographic investigation of circulation in the middle cerebral artery (MCA), heart rate and cost-effect estimation. RESULTS: Combined low-dose treatment with amlodipin and lisinopril for 12 weeks allowed achievement of target blood pressure in more patients and lower systolic and diastolic blood pressure than monotherapy with each of the drugs. There was also a positive effect on E/A index, ERVD, MCA circulation. CONCLUSION: Low-dose combined treatment with lisinopril and amlodipin is more effective and cost-efficient. Moreover, lisinopril addition to amlodipin corrects side effects of amlodipin on central nervous system.     

Experience with a provocative test of calcitonin release as a prospective screening for preclinical medullary thyroid carcinoma in MEN type 2A family members.

We report our experience with a provocative test of calcitonin (CT) release using a combined stimulus of intravenous 10% CaCl2 solution and pentagastrin on 34 normal adults (15 females: age 41 +/- 12.3 years and range 22-65 years; and 19 males: age 43 +/- 9.1 years and range 23-60 years) and in 44 family members of three proven multiple endocrine neoplasia type 2A syndrome (MEN 2A) patients. A commercial radioimmunoassay was used to determine the serum CT levels. Peak CT levels were reached within 2 to 5 minutes after administration of the stimulus in all subjects tested. In the group of normal subjects there was no significant difference in the mean basal CT levels between males (54.8 +/- 21.7 pg/ml) and females (56.5 +/- 34.8 pg/ml), whilst the mean peak response values for males was 146.3 +/- 120.6 pg/ml, which was significantly different from the mean value of females, namely 71.6 +/- 39.0 pg/ml. We did not find significant correlations between the basal CT level, peak CT response, and age. Of the 44 family members tested, 9 showed an exaggerated CT response to the combined stimulus and subsequently had a total thyroidectomy. Histological examination confirmed C-cell hyperplasia (CCH) in one and medullary thyroid carcinoma (MTC) in the other 8. Three of the 9 had high basal plasma CT levels. The 9 patients were retested postoperatively and all showed a flat response to the combined stimulus. Those family members with histological proof of MTC or CCH were screened for genetic linkage to the disease gene for MEN 2A using probe MCK2, and showed correlation in each instance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Affection of cardiovascular system in antiphospholipid syndrome with non-bacterial thrombotic endocarditis

AIM: To study characteristics of cardiovascular affection in antiphospholipid syndrome (APS) with nonbacterial thrombotic endocarditis (NBTE). MATERIAL AND METHODS: The trial included 28 patients with APS and NBTE (26 females, mean age 44 <+/- 13 years). Primary APS was diagnosed in 21 patients, secondary APS associated with systemic lupus erythematosus--in 7 patients. Transthoracic echocardiography was performed in all the patients, transesophageal echocardiography--in 86% of them. Statistic processing was made with logistic regression analysis. RESULTS: All the patients had structural valvular changes: leaflet thickening, sclerosis, vegetations, focuses of calcinosis and valvular dysfunction. Vegetations located on mitral and aortic valves in 64% and occurred on damaged heart valves in 36% patients. An important problem in APS with NBTE was systemic embolism (54%), especially with involvement of central nervous system. Logistic regression revealed association of NBTE with structural changes of aortic and mitral valves, myocardial focal fibrosis and valvular insufficiency. CONCLUSION: APS with NBTE is characterized by absolute predominance of valvular heart lesion with vegetations location on the left heart valves and high risk of embolic complications.     

Theophylline pharmacokinetics in adolescent females following coadministration of oral contraceptives

The influence of 3-9 months of combined low dose oral contraceptives on theophylline pharmacokinetics was studied in 10 adolescent females (age 15-18 years, mean +/- SD 17 +/- 1) and compared to 10 age-matched control subjects (age 13.8-19 years, mean +/- SD 16.5 +/- 1.6). The distribution volume (0.44 +/- 0.06 L/kg in control vs. 0.44 +/- 0.09 L/kg oral contraceptive group), total body clearance (0.78 +/- 0.13 ml/kg/min vs 0.78 +/- 0.18 ml/kg/min) and elimination T 1/2 (402 +/- 78 min vs. 409 +/- 126 min) were identical in the two groups. It appears that during the first 3-9 months of low dose oral contraceptive treatment, these steroids do not alter the pharmacokinetic behaviour of theophylline in adolescent females.     

Survival and prognostic factors of death risk in antiphospholipid syndrome: results of 8-year follow-up

AIM: To evaluate survival and mortality in antiphospholipid syndrome (APS) as well as prognostic factors of APS deterioration. MATERIAL AND METHODS: We retrospectively studied 248 case histories of patients admitted to the Institute of Rheumatology for 8 years. Primary APS was diagnosed in 35 patients, SLE + APS (according to criteria of ACR, 1982)--in 122 patients and SLE without APS--in 91 patients. Mean age was 31.2 +/- 15.0 years (range from 14 to 63), median length of follow-up from the time of diagnosis was 11.9 +/- 5.4 years. During 8 year period all the patients annually and the latest 5 years at least twice a year were examined for the presence of IgG and IgM-anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). Thrombotic events were verified with special techniques. RESULTS: Thirty-eight patients (15%) died during the follow-up period. Mean age of the decreased was 35.4 +/- 12.2 years (range 21-52 years) and the disease duration 8.6 +/- 8.2 years (range 0.6-20), the median length of the survival from the time of the diagnosis was 6.2 +/- 4.3 years. The 8-year survival for SLE patients without APS was 98%, for those with SLE + APS-75% and for patients with primary APS-83%. The presence of APS in SLE patients was significantly associated with high mortality (chi 2 = 12.3, freedom = 4, p = 0.006). Cox regression analysis revealed that the activity of the disease at onset, arterial thrombosis, especially recurrent, thrombocytopenia, valvular disease of the heart, capillaritis, digital necrosis and nephritis were independent risk factors for mortality (p < 0.05). CONCLUSION: Thus, long-term follow-up is necessary for patients with antiphospholipid antibodies especially with APS which lowers survival of SLE patients. Such patients need early corrective therapy to prevent thrombotic events.     

The role of hyperhomocysteinemia in systemic lupus erythematosus and antiphospholipid syndrome

AIM: To assess the role of hyperhomocysteinemia (HHC) in development of vascular complications in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A total of 125 participants (24 males and 101 females aged 38 +/- 13 years) were divided into three groups: group 1--SLE patients (n=51); group 2--SLE+APS patients (n=49); group 3--primary APS patients (n=25). The patients had the disease for 14 +/- 11 years. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) marked APS serologically. Homocystein (HC) was assayed by high performance liquid chromatography. HHC (HC > 15 mcg/l) was diagnosed in 82 of 125 (66%) patients: in 59% patients of group 1, 67%--of group 2 and 76%--of group 3. There was a relationship between HHC and digital necrosis (DN): 80% of DN patients had HHC while HHC was diagnosed in 57% patients free of DN (chi-square = 4.76, p = 0.03). Development of occlusions in APS was associated with HHC. Elevated levels of HC in blood was registered in 43 of 55 (78%) APS patients with thromboses vs. 9 of 19 (47%) patients with APS free of thromboses (p = 0.03). HHC occurred significantly more frequently in patients with arterial thromboses (in all 14 patients) than in patients with venous thromboses (in 16 of 23--69.6%, p = 0.03) and in the absence of thromboses (in 9 of 19, 47.4%, p = 0.04). HHC was associated with thromboses of cerebral, peripheral arteries (90 vs. 47% in patients without thrombosis, p = 0.005; 84 vs. 47%, p = 0.04, respectively), coronary vessels (79 vs. 47%, p = 0.04). In APS patients having arterial thromboses with duration of postthrombocytic period (PTP), estimated as time from thrombosis to entering the trial, less than 2 months, HC concentration was significantly higher (22.9 +/- 7.0 mcg/l) compared to patients with PTP more than 2 years (16.6 +/- 3.7 mcg/l (p = 0.04). CONCLUSION: More than 50% patients with SLE and APS, irrespective of APS variants, had an elevated HC level in the blood. Correlation between HHC and development of thromboses, primarily arterial, in APS gives grounds for the role of HHC in development of vascular complications in SLE and APS.     

The lipid-protein indices of the blood cholesterol transport system in systemic lupus erythematosus]

AIM: To assess parameters of blood cholesterol lipid-protein spectrum and characteristics of blood cholesterol (C) transport system in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Lipid-protein blood spectrum was studied in 60 patients (45 females and 15 males) with verified SLE aged 15-44 years (mean age 28.9 +/- 8.1 years). The duration of the disease varied from 2 months to 28 years (mean 8.6 +/- 6.6 years). SLE course and activity were defined according to V. A. Nasonova's classification. The control patients (35 healthy subjects) were matched by age (30.0 +/- 6.1 years) and gender (27 females and 8 males). RESULTS: Elevated levels of C and C of low-density lipoproteins (LDLP), triglycerides (TG) were found in 35% and 30% of patients, respectively. C of high-density lipoproteins (HDLP) was low in 32% of patients. HDLP phospholipids were also subnormal, their proportion changed: concentrations of phosphatidylcholine were low, those of lisophosphatidylcholine, sphingomyelin, diethanolamine, cardiolipin were higher than in the controls. TG and proportion apo/B/AI were higher, content of HDLP components low in patients with the disease duration up to 5 years. Patients with highly and moderately active SLE had high levels of TG, apo/B, apo/B/apo/AI, low levels of HDLP C, apo/AI and HDLP phospholipids. CONCLUSION: Marked dyslipidemias were detected in 1/3 of SLE patients. Cholesterol transport changes arise at early SLE stages. Alterations in the blood lipid-protein spectrum appeared more pronounced and atherogenic in maximal SLE activity. Quantitative and qualitative shifts in HDLP composition induce changes in antiatherogenic properties of relevant lipoproteins in SLE patients.     

Periarthritis of the shoulder joint: variants of the course and treatment with artrofoon

AIM: To compare efficacy of shoulder joint periarthritis (SJP) treatment with artrofoon vs non-steroid anti-inflammatory drugs (NSAID). MATERIAL AND METHODS: SJP patients of the study group (12 males, 18 females, mean age 59.4 +/- 8.9 years, the disease duration 6.5 +/- 3.8 years) received artrofoon (1 tablet 8 times a day for 3 months, in improvement of the condition the dose was reduced to 4 tablets a day). Patients of the control group (11 males, 19 females, mean age 58.3 +/- 9.6 years, the disease duration 5.1 +/- 4.1 years) were given NSAID (primarily diclofenac in a dose 100 mg/day with subsequent dose reduction in improvement). All the patients were examined on the day of the treatment start, 2 weeks, 1 and 3 months later. The examination protocol included general examination, measurement of blood pressure, body mass, height, pain at rest and exercise, motility of the shoulder joint, subjective and objective efficacy and tolerance of the drugs. Total blood count, biochemical blood analysis, urine test, ECG, x-ray, ultrasound investigation of the joint were performed before and after therapy. RESULTS: The majority of the patients from both groups experienced nocturnal pain relief, artrofoon relived also pain at the joint movement. Significant objective and subjective responses were registered in 15 and 14, partial response--in 10 and 12 patients of the study group, respectively, no response--in 5 and 4 patients, respectively. In the controls, the above degree of the response was in 9 and 12, 18 and 16, 3 and 2 patients, respectively. Negative effects of the treatments were not seen. CONCLUSION: SJP treatment with artrofoon is effective. It relieves pain, improves motility of the joint, normalizes mental and somatic status of the patients.     

Spirapril - a new long-acting ACE inhibitor: efficacy and safety in patients with arterial hypertension in combination with diabetes mellitus and impaired kidney function

AIM: To examine effectiveness and safety of quadropril. MATERIAL AND METHODS: Changes in blood pressure (BP), heart rate (HR), levels of glucose, potassium and creatinine, creatinine clearance were studied in 120 patients (48 males and 72 females, mean age 60.6 +/- 0.7 years) with mild to moderate arterial hypertension (AH) with average duration 13.8 +/- 0.7 years. The patients were divided into 3 groups: with AH (n = 40), AH + noninsulindependent diabetes mellitus (DM) (n = 43), AH and nephropathy (n = 37). 8-week treatment was performed with a standard dose of 6 mg/day (1 tablet of quadropril). Control examinations were made 2, 4 and 8 weeks after the treatment. RESULTS: After 8 weeks of treatment a decrease in systolic blood pressure in AH group was 24.0 +/- 3.0 mm Hg and in diastolic blood pressure 16.3 +/- 1.3 mm Hg (P < 0.001). In the group with DM this decrease was 22.4 +/- 2.8 mm Hg and 15.7 +/- 1.4 mm Hg (p < 0.001), respectively. In the group with nephropathy this decrease was 26.4 +/- 2.4 and 16.5 +/- 1.3 mm Hg (p < 0.001), respectively. Heart rate changed significantly only in diabetics: from 75.1 +/- 1.7 to 72.9 +/- 1.3 beats/min. Biochemical parameters in the hypertensive and diabetic patients did not change significantly. In the nephropathy group there was a significant decrease in creatinine and increase in creatinine clearance. Their level of glucose and potassium changed insignificantly. CONCLUSION: The treatment with quadropril results in a significant decrease in blood pressure, does not influence parameters of carbohydrate metabolism, improves nitrogen eliminating function of the kidneys.     

The role of psychopharmacotherapy in combined treatment of patients with metabolic syndrome and depression

AIM: To evaluate efficacy and tolerance of combined treatment with antidepressant cipramil in patients with metabolic syndrome (MS). MATERIAL AND METHODS: We examined 23 MS patients with depression (mean age 47 +/- 7.4 years). For diagnosis and somatic state evaluation we used clinical, device and laboratory tests. The clinicopsychopathological method, MADRS and CGI scales were applied for assessment of mental state and treatment efficacy. RESULTS: We achieved positive effects of 12-week combined somatotropic and psychotropic therapy on carbohydrate metabolism: a significant decrease of fasting blood glucose from 6.6 +/- 1.4 to 6.2 +/- 0.7 mmol and postprandial (2 hours after meal) glucose from 8.6 +/- 1.5 to 7.8 +/- 0.8 mmol/l, of waist circumference from 106.0 +/- 11.93 to 103.5 +/- 12.3 cm, body mass index from 32.5 +/- 4.54 to 31.4 +/- 4.76 kg m2, systolic blood pressure from 154.52 +/- 7.4 to 137.91 +/- 13.8 mm Hg and diastolic blood pressure from 90.1 +/- 6.2 to 81.0 +/- 6.6 mm Hg. A significant change in the levels of total cholesterol and triglycerides was not registered. CONCLUSION: Administration of antidepressant in MS patients relieved depression. This improved carbohydrate metabolism, lowered blood pressure and body mass index.     

A multicentre study of abdominal aorta diameters in a Turkish population

The aim of this study was to determine the normal values for aortic diameters and the prevalence of aortic dilatation in a mixed Turkish population. Between March 1998 and May 2000, patients who were undergoing abdominal ultrasonography examination for pathologies not involving the aorta, in three different cities, were enrolled into the study prospectively. The anterior posterior aortic diameters were measured at the subdiaphragmatic and aortic bifurcation levels using ultrasonography. A total of 596 patients were included (302 females, 294 males). The mean age was 48 +/- 16 years (range, 6-88 years). The mean aortic diameter in the whole group was 19.0 +/- 3.9 mm (10-45 mm) at the subdiaphragmatic level and 15.7 +/- 3.6 mm (9-65 mm) at the aortic bifurcation level. The mean subdiaphragmatic aortic diameter was 18 +/- 3 mm in females and 19 +/- 4 mm in males. The mean aortic diameters at the bifurcation level was 15 +/- 3 mm in females and 16 +/- 4 mm in males. An aortic bifurcation diameter > 30 mm was encountered in 0.67% of the population. This ratio increased to 1.8% in patients over 55 years of age, regardless of sex. A subdiaphragmatic aorta diameter above 30 mm was observed in 1.2% of the population. In patients over the age of 55 years, this ratio increased to 2.7% (3.6% in males and 1.9% in females). In this national study, the subdiaphragmatic aortic diameters were similar to mean values reported in the world literature. The mean aortic bifurcation diameters were generally lower when compared with the literature, which may be due to difficulties in standardization of the measurements. Aneurysmal dilatation rates in this study also conform to those reported in studies conducted in other countries. Considering the significant number of patients with aneurysmal dilatation of the aorta in the elderly population, we believe it would be prudent to evaluate the aorta in all patients undergoing abdominal ultrasonographic examination.     

Time-wise sequential analysis of gastric aspirate for occult blood and pH in sick preterm infants

Improvements in both care and technology have led to the survival of more low birthweight infants. Initially, these infants are not fed orally and are placed on parenteral nutrition. In an attempt to evaluate sequential time-wise changes in gastric pH and occult blood loss, evaluation of gastric pH and tests for the presence of blood in the gastric aspirate were carried out in two groups of infants. Group 1 consisted of seven cases, three males and four females, with a mean +/- SE gestation of 29.9 +/- 0.8 weeks and a birthweight of 1410 +/- 190 g. Group 2 consisted of nine cases, three males and six females, with a mean +/- gestation of 28.6 +/- 0.84 weeks and a birthweight of 940 +/- 120 g. Gastric contents were sampled through indwelling orogastric tubes every 4-6 h daily for the first seven days in Group 1 and 14 days in Group 2. Infants in Group 1 were spontaneously breathing with mild hyaline membrane disease (HMD) whereas Group 2 infants had severe HMD requiring ventilation. Results indicate that critically ill preterm infants (Group 2) had significantly lower pH when compared to Group 1 (p less than 0.015). Progressive decrease in pH was observed in both groups (P less than 0.001). The association of occult gastric blood loss with decreasing pH was examined using pooled data from both groups of neonates. During the times when bleeding occurred, the mean +/- SE gastric pH level was 2 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of hypoalbuminemia with a low level of dehydroepiandrosteron sulphate in blood serum of patients during chronic hemodialysis

AIM: To study dehydroepiandrosterone sulphate (DEA-S) in patients on chronic hemodialysis (HD) and its correlation with body mass and serum albumin. MATERIAL AND METHODS: DEA-S and cortisol in the serum were measured at enzyme immunoassay (EIA) in 124 patients (56 males, 68 females, mean age 47+/-12 years) on chronic HD. HD was made for 4 hours, on the average, 3 times a week using bicarbonate solution for dialysis. DEA-S and cortisol in blood serum were measured with EIA. RESULTS: A DEA-S level was higher in males than in females (7.6+/-5.3 and 3.4 +/-2.7 mcmol/l, respectively, p < 0.001). A negative correlation was found between the age and content of DEA-S (r = -0.36; p < 0.001). No correlation was established between DEA-S and cortisol content in blood serum (r-0.06; p = 0.6). Serum albumin was less in patients with low DEA-S. The multifactorial regression analysis showed an independent direct relationship between the levels of DEA-S and albumin in blood serum. CONCLUSION: DEA-S levels in HD patients depend on gender and age. The hormone concentrations are higher in males. Hypoalbuminemia in HD patients is associated with low DEA-S in blood serum.     

Types of lupus nephritis exacerbations: prognostic significance

AIM: To characterize the course of lupus nephritis (LN) in terms of demographic indices (sex, age of renal disease onset), the presence of antiphospholipid syndrome (APS) and to ascertain a prognostic role of the disease exacerbations. MATERIAL AND METHODS: A total of 121 LN patients were followed up from 1997 to 2004 (mean duration of the follow-up 5.6 +/- 6.4 years). A LN course was characterized by the presence of a complete or partial remission, exacerbation of the disease, repeated hospitalisations. Two types of exacerbations were considered: proteinuric, running with progressive proteinuria and normal renal function (type 1); functional, running with elevation of blood creatinine (type 2). RESULTS: Exacerbations were observed in one third of the examinees, 70% of them ran with renal dysfunction. Exacerbations occurred more frequently in males than in females (50 vs 27%, respectively; p = 0.08) and in patients with early onset of LN (at the age of 40 years and younger, 80 vs 60%, respectively; p < 0.05). Exacerbations of type 2 occurred in males, in patients with early onset of renal damage and in APS association. It is shown that LN exacerbations, their incidence and type (a functional type) have a negative influence on renal survival of the patients. CONCLUSION: Identification of groups of LN patients at high risk of exacerbations and unfavourable prognostic role of exacerbations dictates the necessity of due immunosuppressive therapy for maintenance of remission.     

Folate and vitamin B12-deficiency anemias in Vietnamese immigrants living in Southern California

BACKGROUND: Although the occurrence of iron deficiency anemia and hemoglobinopathies in Vietnamese immigrants has been reported, folate and vitamin B12 deficiencies have not. Proper diagnosis and effective treatment is necessary to achieve a complete correction of anemia. METHODS: We retrospectively analyzed the records of Vietnamese immigrants seen in our medical clinic from 1991 to 1993. Fifty-nine anemic patients (48 females and 11 males) had low levels of red blood cell (RBC) folate and/or serum vitamin B12. RESULTS: The patients' mean age was 37.7+/-17 years. Mean hemoglobin and hematocrit values were 11.4+/-0.7 g/dL and 34.4%+/-2.2%, respectively. Mean corpuscular volume (MCV) was normal in 40 patients (68%) (mean, 89.1+/-5 fL) and low in 19 patients (32%) (mean, 69.7+/-6 fL). Forty-four patients had low RBC folate levels (mean, 157.7+/-41.7 ng/mL). Twenty patients had low serum vitamin B12 levels (mean, 165.6+/-47 pg/mL). Fourteen patients had ferritin levels of <20%. CONCLUSIONS: Concomitant folate, vitamin B12, and iron deficiencies or hemoglobinopathies might have been responsible for either normal or low MCV in some of our anemic patients. In this ethnic group, RBC folate and serum vitamin B12 levels should be determined in all anemic patients.     

Glycemic control with Humalog Mix25 in type 2 diabetes inadequately controlled with glyburide.

BACKGROUND: Humalog Mix25 (Mix25) is a premixed insulin mixture of 25% insulin lispro and 75% neutral protamine lispro. OBJECTIVE: The aim of this study was to quantitate the improvement in glycemic control achieved with Mix25 versus the maximum dose of glyburide (GB) in patients with type 2 diabetes inadequately controlled with GB. METHODS: In this randomized, parallel, open-label comparative study, patients with type 2 diabetes received either Mix25 before the morning and evening meals for 4 months or GB 15 mg daily for 4 months. Glycemic control was assessed by glycosylated hemoglobin (HbA1c) measurements, 4-point self-monitored blood glucose profiles, and patient-reported hypoglycemia. Patients also completed a treatment satisfaction questionnaire at the end of the study. RESULTS: All 172 patients were white; 85 were randomized to receive Mix25. The mean age was 59.5 +/- 8.2 years, and 35.5% (61/172) were men. The mean body mass index was 27.2 kg/m2. The mean duration of type 2 diabetes was 10.2 +/- 6.6 years, and the mean duration of sulfonylurea treatment was 5.8 +/- 5.9 years. The mean HbA1c and fasting blood glucose levels were 10.07% +/- 1.4% and 11.6 +/- 2.8 mmol/L, respectively, in the glyburide group and 9.85% +/- 1.2% and 12.2 +/- 2.9 mmol/L, respectively, in the Mix25 group. There were no statistically significant differences between the treatment groups at baseline for any of the demographic or efficacy variables. At end point, mean HbA1c was significantly lower in the Mix25 group than in the GB group (Mix25, 8.5% +/- 1.3%; GB, 9.4% +/- 1.8%; P = 0.001). A larger decrease from baseline in HbA1c and in all self-monitored blood glucose values was observed in the Mix25 group: -1.4% versus -0.7% for HbA1c, P = 0.004; -2.8 mmol/L versus -1.1 mmol/L for fasting blood glucose, P < 0.01; -5.1 mmol/L versus -1.7 mmol/L for the morning 2-hour postprandial blood glucose, P < 0.001; -2.2 mmol/L versus -0.8 mmol/L for the evening preprandial blood glucose, P < 0.05; and -4.4 mmol/L versus -1.5 mmol/L for the evening 2-hour postprandial blood glucose, P < 0.001. Patients expressed more satisfaction with Mix25 than with GB, as measured by the weighted combined score on a treatment satisfaction questionnaire (2.0 +/- 1.3 vs 0.7 +/- 1.3). The mean hypoglycemia rate (events per patient per 30 days) was significantly higher in the Mix25 group at end point (Mix25, 0.30 +/- 0.53; GB, 0.05 +/- 0.20; P < 0.001). CONCLUSIONS: Compared with maximum-dose GB, twice-daily injections of Mix25 resulted in improved glycemic control and treatment satisfaction, and were associated with a predictably higher rate of hypoglycemia in this group of patients with type 2 diabetes who were inadequately controlled with maximum-dose GB. Although the inclusion of patients who were inadequately controlled with GB was intended to allow a comparison of the 2 treatments with respect to efficacy and tolerability in a real-life setting, a double-blind comparison in treatment-naive individuals may have resulted in a different outcome.     

Osteonecroses in systemic lupus erythematosus and antiphospholipid syndrome

The purpose of the study was to analyze the incidence of osteonecroses (ON) in systemic lupus erythematosus (SLE) patients with and without antiphospholipid syndrome (APS), primary APS (PAPS) and to define a relationship of the development of ON to some risk factors for vascular diseases. The study included 369 patients, including 293 with SLE, 160 with secondary APS, 76 with PAPS. The patients aged 14 to 63 years (mean 31.9+/-10.9 years). The history of disease was 0.6 to 30 years (mean 9.1+/-7.5 years). Among them 32 (8.7%) patients with aseptic necroses of different bones were selected in accordance with the data of X-ray studies. ON was detected in 8.7 patients with SLE and APS. The X-ray signs corresponded to third-to-sixth-degree ON. The most common site of ON was the head of the femur, although another site of ON was observed and multiple ON was typical. Leukopenia, creatininemia, fibrinogen levels were associated with ON (p < 0.05 by the Mann-Whitney test). The activity of SLE was significantly associated with SLEDAI scale scores (p < 0.05 by the Wald-Wolfovitz test). Six patients with SLE and ON had high scores by this scale--more than 40 scores of the maximum 150 possible scores. APS was diagnosed in 87.5 of the patients with ON (28 of the 32 patients) and only in 61.7% of the patients without ON (in 208 of the 337 patients) (chi2 = 8.4; p = 0.004). The development of ON in the examinees was significantly associated with the presence of APS. The activity of SLE, particularly nephritis, arthritis, positive tests for phospholipid antibodies, the presence of arterial thromboses, thrombocytopenia at the height of disease, therapy with large doses of glucocorticoids.     

Blockers of angiotensin receptors: a novel approach to the treatment of secondary pulmonary hypertension

AIM: To evaluate efficacy of losartan, a blocker of angiotensin receptors, in combined treatment of secondary pulmonary hypertension (SPH) in patients with chronic obstructive bronchitis (COB). MATERIAL AND METHODS: Losartan effects on hemodynamics, blood gases and clinical course of the disease were studied in 29 patients with COB and SPH (mean age 52 +/- 1.7 years). A control group consisted of 15 patients (mean age 51 +/- 1.5 years) treated with cardiac glycosides and diuretic drugs. M- and B-mode Doppler echocardiography registered hemodynamic parameters. 24-h monitoring of AP and ECG were made by standard methods. Blood gases and venous rheology were examined. RESULTS: Losartan administration in COB patients with SPH improved hemodynamics. Stroke index rose from 36.3 +/- 2.1 to 45.8 +/- 2.1 ml/m2 (by 26.2%, p < 0.01) in SPH functional class III, from 26.3 +/- 1.9 to 32.7 +/- 2.1 ml/m2 (by 24.3%, p < 0.01) in functional class IV Cardiac index rose by 22.2 and 21.1%, respectively. Pulmonary hemodynamics improved too: systolic pressure in pulmonary artery fell by 25.7% in functional class III, by 18.6% in functional class IV. Losartan normalized a 24-h AP profile, reduced the number of painless myocardial ischemia. CONCLUSION: Use of losartan in combined therapy of patients with COB and SPH improves clinical status of the patients, corrects basic cardiohemodynamic parameters, has a positive effect on AP profiles without negative impact on blood gas composition and rheology.