PubMed Health⌕ Search

Biomedical subjects

Z Milicevic

Publications and source records attributed to Z Milicevic.

14 recordsLinked to original sources
PubMed2004

Beta-cell secretory function and CD25 + lymphocyte subsets in the early stage of type 1 diabetes mellitus.

Cellular immunologic tests have not been used for diagnostic purposes in individuals at risk for autoimmune insulitis or in patients with partial beta-cell destruction because of a lack of studies that show their predictive value. In this study we initially evaluated 43 patients with recent-onset Type 1 diabetes (disease duration <or= 6 months, 29 ICA positive) with regard to beta-cell secretion stimulation test with glucagon and immunologic parameters, including CD4 +, CD8 +, CD4 + CD25 +, CD8 + CD25 + lymphocyte subsets. At baseline, C-peptide concentration 6 min after stimulation increased on average by 0.18 +/- 0.27 micro g/ml. The percentage of CD4 + cells was 42 +/- 9,4 % (healthy controls 44 +/- 7.3 %, p nonsig.) and percentage of CD8 + was 33 +/- 8.6 % (healthy control 31 +/- 8.3 %, p nonsig.). Relative size of CD4 + CD25 + subpopulation was 7 +/- 5.4 % (healthy control 2 +/- 2 %, p < 0.001). Percentage of activated CD8 + cell subset was also increased (2 +/- 1.4 vs. 1.0 +/- 1.0 %), but not significantly. Functional beta-cell testing was repeated after 6 months and nineteen patients were eligible for analysis. Their response was weaker after 6 months (0.13 +/- 0.1 micro g/ml, p < 0.05 vs. baseline). The average change in C-peptide excursion from baseline to the endpoint was - 0.07 +/- 0.17 micro g/ml. There was no significant correlation between beta-cell functional parameters at baseline (C-peptide6min (baseline)) and the relative size of various T cell subpopulations. Results were identical for the 6-month beta-cell functional data (C-peptide6min (6month)). The change in the excursion of C-peptide between baseline and follow-up visit (C-peptide6min (6month-baseline)) showed mild, negative correlation with relative size of the CD8 + CD25 + subpopulation (r = - 0.511, p = 0.025), which may indicate that the size of this cell subpopulation has predictive value in assessing future functional beta-cell changes.

Adolescent↗
PubMed2003

Interventions in diabetic patients after myocardial infarction.

Occurrence of a first acute myocardial infarction (AMI) is associated with further increase in risk of cardiovascular events. This risk is further increase is disproportionate in diabetics, who suffer from very high mortality short and long term after AMI. Factors responsible for the increased risk are only partially understood. Additional, properly designed, prospective epidemiological studies are needed for a better understanding of complicated diabetic macrovascular disease after the occurrence of the first event. These studies are also needed for designing interventional trials that target factors that carry the highest risk of new events. Published studies provide some insight into the issue of efficacy of blood pressure, cholesterol and blood glucose lowering strategies in the diabetic population. It remains unclear how important is the control of triglyceride concentration or other risk factors during various stages of recovery after AMI. The main reason is the lack of clinical trials. Evidence-based approach to patients with diabetes and AMI indicates the importance of tight control of cholesterol, blood pressure and blood glucose concentration. Although other risk factors have not been extensively studied, it is reasonable to assume that other major risk factors, such as hypertriglyceridemia, should be targeted as well. In the meantime, more data need to be collected from prospective epidemiological and interventional protocols, if better control over the cardiovascular risk in this high-risk population is to be achieved.

Anticholesteremic Agents↗
PubMed2003

Retrospective analysis of cardiovascular outcomes in patients with type 2 diabetes mellitus after the first acute myocardial infarction.

We retrospectively analyzed survival in patients with type 2 diabetes mellitus (DM) after first acute myocardial infarction (AMI). The study was conducted in 5 sites in Poland and involved 521 patients who survived more than 30 days after AMI. In the 5-year period after the acute event, we investigated the following cardiovascular (CV) outcomes: death (overall mortality), next MI, stroke, hospitalization due to acute coronary symptoms (HACS), and composite outcomes (whichever occurred first). We also assessed: age, smoking habit, obesity, hypertension, dyslipidemia and coronary artery disease (CAD) diagnosed before AMI, and gender. 269 patients (52%) suffered one of the outcomes from the composite CV endpoint. HACS was the first event in 164 cases, MI in 59, death in 32, and stroke in 14 patients. Analyzing the prevalence of individual CV events, we found: HACS in 184 patients (35%), next MI in 79 patients (15%), death in 59 patients (11%), and stroke in 30 patients (6%). Only dyslipidemia, arterial hypertension, and CAD were independent risk factors with an impact on composite CV endpoint. Other analyzed risk factors like smoking and obesity did not have independent effects on the CV risk. In the retrospective analysis, we found that HACS was the most frequent CV event in individuals with type 2 DM after AMI. The CV risk in type 2 diabetics who suffered at least one myocardial infarction was further increased in those with coexisting dyslipidemia, arterial hypertension or CAD. These findings support the current guidelines which recommend aggressive management of CV risk factors including hypertension, dyslipidemia and CAD before a first myocardial infarction.

Diabetes Mellitus, Type 2↗
PubMed2003

A comparison of insulin lispro Mix25 and human insulin 30/70 in the treatment of type 2 diabetes during Ramadan.

OBJECTIVE: To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning and evening postprandial glucose (PPG) control, and on average daily blood-glucose (BG), in patients with Type 2 diabetes who wish to fast during Ramadan. METHOD: Insulin lispro Mix25 and human insulin 30/70 were compared in an open-label, multicenter, randomised, crossover study involving 151 patients. Each treatment period had a duration of 14 days during which the patients self-monitored their BG before and 2 h after the main meals on any 3 days within the last 5 days of each treatment period. RESULTS: The 2 h PPG excursion following the main evening meal after sunset was significantly lower with insulin lispro Mix25 (3.4+/-2.9 mmol/l) compared with human insulin 30/70 (4.0+/-3.2 mmol/l, P=0.007). The evening pre-meal fasting BG values were also lower with insulin lispro Mix25 (7.1+/-2.2 mmol/l) versus human insulin 30/70 (7.5+/-2.6 mmol/l, P=0.034). The average daily BG concentration was 9.5+/-2.4 mmol/l during treatment with insulin lispro Mix25 versus 10.1+/-2.5 mmol/l with human insulin 30/70 given in identical doses (P=0.004). CONCLUSION: When compared with human insulin 30/70, treatment of insulin-requiring Type 2 patients with insulin lispro Mix25 during Ramadan resulted in better average daily glycaemia, and better BG control before and after the evening meal. Insulin lispro Mix25 should be considered as a therapeutic option during Ramadan.

Blood Glucose↗
PubMed2003

Humalog Mix 25 in patients with type 2 diabetes which do not achieve acceptable glycemic control with oral agents: results from a phase III, randomized, parallel study.

BACKGROUND: Humalog Mix 25 (Mix 25) is a premixed insulin mixture of 25% lispro and 75% neutral protamine lispro. Insulin lispro is an analog of human insulin. It is created when the amino acids at positions 28 and 29 of the B-chain of insulin are reversed. The natural sequence in human insulin at this position is proline at B28 and lysine at B29. The pharmacokinetic and pharmacodynamic profiles of insulin lispro indicate that it is more rapid acting, and therefore more physiological mealtime insulin than regular human insulin. OBJECTIVE: Primary objective of this study was to compare twice daily treatment with insulin lispro low mixture (Mix 25) to oral treatment with glibenclamide in patients with type 2 diabetes, with respect to the mean 2-hour postprandial blood glucose excursions after breakfast and dinner. SECONDARY OBJECTIVES: to compare the two treatments with regard to the following: hemoglobin A1c, fasting blood glucose, pre-dinner blood glucose, frequency of hypoglycemia, body weight, treatment satisfaction (by questionnaire). METHODS: The study described is a randomized, open-label, parallel group comparison of two treatment regimens in patients with type 2 diabetes. The study included two periods. The lead-in period lasted 10 +/- 7 days, all patients were taking glibenclamide. The treatment period lasted 16 weeks. Patients were randomized to receive either glibenclamide 15 mg daily or switch to Mix 25 before breakfast and dinner. Study design is illustrated in Fig. 1. Glycemic control was assessed by glycosylated hemoglobin (HbA1c) measurements, 4-point self monitoring blood glucose profiles, and patient reported hypoglycemia. One treatment satisfaction questionnaire (Appendix 1) was completed by each participant. RESULTS: 175 patients were included from the two participating countries (Romania--100 patients and Russia--75 patients). 85 were randomized to receive Mix 25 and 90 to glibenclamide arm. 172 patients were included in the efficacy analysis. Baseline patient characteristics did not show any differences between treatment groups for any of the demographic (age, gender, height, body weight, body mass index) or efficacy parameters (HbA1c or self monitored BG values). 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 glibenclamide group and 9.85 +/- 1.2% and 12.2 +/- 2.9 mmol/L, respectively, in the Mix 25 group. At the end point, all efficacy parameters were better improved in Mix 25 group (HbA1c, fasting blood glucose, 2-hour postprandial blood glucose). Mean HbA1c was significantly lower in the Mix 25 group than in the GB group (Mix 25, 8.5% +/- 1.3%; GB, 9.4 +/- 1.8%; P = 0.001). For all self-monitored blood glucose values (Fig. 2) a larger decrease from baseline was observed in the Mix 25 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). Percentage of patients experiencing at least 1 episode of hypoglycemia was--as predicted--higher in the Mix 25 group (44.7% versus 10.3%; P = 0.01). Patients expressed more satisfaction with Mix 25 than with GB, as measured by the weighted combined score on a treatment satisfaction questionnaire (2.0 +/- 1.3 vs 0.7 +/- 1.3). CONCLUSIONS: When glycemic control can no longer be achieved by oral antidiabetic agents, treatment with insulin should be considered as the next therapeutic option. Mix 25 provided good overall glycemic control, as well as patient treatment satisfaction.

Administration, Oral↗
PubMed2001

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.

Aged↗
PubMed2001

Intramuscular injection of insulin lispro or soluble human insulin: pharmacokinetics and glucodynamics in Type 2 diabetes.

AIM: The aim of the study was to compare the pharmacokinetics and glucodynamics of insulin lispro and soluble human insulin following intramuscular (i.m.) injection in patients with Type 2 diabetes with secondary failure of sulphonylureas. METHODS: Single 15-U i.m. doses of insulin lispro or soluble human insulin were administered to 16 patients in a two-way, randomized, crossover design. Glucodynamic and pharmacokinetic parameters were determined over 6 h after insulin injection using clamp techniques. RESULTS: Insulin C(max) was significantly higher (971 +/- 217 vs. 659 +/- 141 pmol/l, P < 0.001) and T(max) was significantly shorter (46.9 +/- 27 vs. 94.7 +/- 50.1 min, P = 0.002) with insulin lispro. Glucose infusion rate (GIR) curves showed clear separation 20 min after injection and were significantly greater for insulin lispro during the 40-60, 60-80 and 80-100-minute time intervals. Total glucose infused was only approximately 5% larger with insulin lispro during the 6-h follow-up, due to lower insulinaemia at later time points. The glucose R(max) and TR(max) were not statistically different between insulin treatments. CONCLUSION: This study shows that i.m. injection of insulin lispro is followed by its more rapid absorption, which results in stronger metabolic effect in the first 2 h when compared with soluble human insulin under the same test conditions. Diabet. Med. 18, 562-566 (2001)

Blood Glucose↗
PubMed2001

Low arylsulphatase A activity in the development of psychiatric disorders.

Previous studies have suggested that arylsulphatase A (ASA) deficiency may be present in psychiatric patients. A number of patients with low ASA activity and various neuropsychiatric symptoms have been observed. Metachromatic leucodystrophy (MLD) is a disease caused by deficiency of the enzyme ASA. Clinically, adult MLD may present as a schizophrenia-like psychosis, deterioration of cognitive functions, personality changes, depression and dementia. However, there are individuals with low ASA activity without clinical symptoms of MLD. This state is described as ASA pseudodeficiency. It remains controversial whether low ASA activity predisposes to or influences the development of psychiatric symptoms. Relatively little attention has been paid to the role of neurodegenerative processes in the pathophysiology of psychiatric disorders. The hypothesis underlying this work is that there is a subclass of mentally ill patients whose psychiatric problems are at least partly caused by an abnormal ASA. The purpose of this particular study was to determine whether an abnormal ASA could be detected in schizophrenic, major depressed and demented patients and control subjects. There were 66 schizophrenic, 59 major depressed and 61 demented patients. The control group consisted of 102 healthy volunteers. Leucocyte ASA activity was determined from blood samples, using p-nitrocatechol sulphate as substrate. Our results show that low ASA activity is more frequently found in psychiatric patients than in control subjects. Our findings indicate that clinical types of major depression and schizophrenia could be connected with low ASA activity. The presence of a decreased ASA activity points to the conclusion that an enzyme deficit entails vulnerability to psychiatric disorders.

Adult↗
PubMed1995

Beyond glycemia.

Explore the source record for details and available documents.

Blood Glucose↗
PubMedDate not supplied

How recombinant insulin analogs improve insulin therapy of diabetes mellitus: pathophysiology, clinical practice and recommendations.

According to the latest prognoses, 300 million people are expected to suffer from diabetes (particularly type 2) in 2025; diabetes will become a new epidemics of the coming century. Therefore it is so important to get acquainted with the pathomechanism of diabetes-related disorders and the possibilities of effective treatment. During the last decade, numerous prospective epidemiological studies have been completed, which have considerably extended our knowledge of the pathomechanism of disturbances and their effect on late complications of diabetes. Resistance to insulin has an important role in the etiology of type 2 diabetes. However, there is substantial evidence indicating that impairment or regression of rapid insulin secretion phase at the early stage of the disease is a factor of no lesser importance. The lack of appropriate insulin concentration after the stimulation by food ingestion (first 30 min after the meal), leads to permanent, treatment-resistant hyperglycemia. The postulated attempts to obtain a 'nearly normoglycemic' condition, as well as the results of prospective epidemiological studies proving that achieving this aim improves the prognosis of diabetic patients, prompt the researchers to search for the drugs or treatment schedules, which could effectively restore the impaired insulin secretion, and its early phase in particular, in type 2 diabetes. Human insulin analogs and their pre-formulated commercially available mixtures seem very promising in this respect.

Adolescent↗
PubMedDate not supplied

Apoptotic versus genotoxic potential of anti-tumor agents: a concept of duality in unity.

Recent advances in anti-tumor therapy have raised a problem of secondary tumors and tumor resistance. Secondary tumors induced by chemotherapeutic agents as a consequence of primary therapy have poor prognostic outcome. Many new insights into molecular controls of cell cycle progression of normal and cancer cells can provide a useful framework in order to identify potential targets for anti-tumor therapies. One of the most promising strategies is the possibility to modulate apoptosis induced by anti-tumor agents. Cancer cell survival after chemotherapy will depend on specific checkpoints and/or repair pathways that have been lost, leading either to greater susceptibility to anti-tumor agents when the repair of damage is most important for survival or to greater resistance when the apoptotic response is more important. We have proposed a hypothesis that views survival and apoptotic processes (duality) in normal and tumor cells as genetically coupled (unity). We introduce, through a theoretical background, a new pathway of apoptotic inhibition. The proposed process of apoptotic inhibition is induced by mutation fixation in which recombination/repair processes (hRAD genes) play an important role. These coupled processes (duality in unity), to our view, underline tumor resistance by apoptotic inhibition and mutation fixation in normal cells exposed to anti-tumor agents.

Antineoplastic Agents↗
PubMedDate not supplied

Colonic vasoactive intestinal polypeptide (VIP) in ulcerative colitis--a radioimmunoassay and immunohistochemical study.

BACKGROUND/AIMS: In this study, we present radioimmunoassay data describing the concentration of Vasoactive Intestinal Polypeptide (VIP) in both plasma and colonic biopsies, as well as immunostaining of VIPergic innervation in mucosal biopsies of normal subjects and patients with ulcerative colitis (UC). PATIENTS AND METHODS: Thirty three patients with UC and 17 healthy subjects were investigated. All UC patients suffered from active disease. Fasting circulating levels of VIP in plasma as well as tissue concentrations were measured by radioimmunoassay. For the immunohistochemistry, polyclonal antibody against VIP and the streptavidin-biotin peroxidase complex technique were carried out. RESULTS: Overall plasma VIP concentrations in the UC patients were similar to those in the controls. Significantly decreased concentrations of VIP were found in UC of rectum compared to the normal tissue. However, both plasma VIP values and tissue concentrations were found to be significantly lower in patients expressing minimal or mild active disease according to clinical activity index (AI) and histological activity index (HAI), but marked increase of plasma VIP was clear in UC patients with moderate or severe AI and HAI. There was a trend towards increased tissue concentrations of VIP in the group of patients with moderate or severe AI and HAI. Our immunohistochemical analysis of VIP fibers and nerve cell bodies revealed consistently weaker VIP-immunoreactivity in the rectum in UC patients with minimal or mild HAI. Simultaneously, in the rectal biopsies from UC patients with moderate and severe disease, the fibers in the lamina propria and ganglion cells in the submucous plexus were markedly increased in density and in degree of immunostaining. Very strong immunoreactivity was also found in inflammatory cells of the lamina propria as well as in the epithelial layer of the biopsies from UC patients with obvious disease. CONCLUSIONS: Our study shows clearly the heterogeneity in the response of VIP plasma level as well as rectum concentration and distribution in UC patients at different stages of the active disease. The possible role of VIP in the colon suggests that further studies of the alterations of this gut peptide may be useful in the understanding of UC pathophysiology.

Adult↗