Serum interleukin-6 predicts cortisol release in acute stroke patients.

Altered hypothalamo-pituitary-adrenal axis was reported in stroke patients; however, mechanisms responsible for this phenomenon are barely understood. Acute cerebral ischemia triggers interleukin-6 (IL-6) release into blood. Circulating IL-6 can stimulate hypothalamo-pituitary-adrenal axis. The goal of our study was to assess a relationship between serum IL-6 and cortisol in acute ischemic stroke. Twenty two patients with ischemic stroke and 17 controls were included. Serum samples were collected on the 2nd day of stroke at 6:00, 10:00 18:00, 22:00 h and at the same time points in control group. Cytokines and cortisol levels were measured using ELISA method. Serum IL-6 and cortisol levels were higher in stroke patients than in controls. Cortisol displayed diurnal variations in both stroke patients and controls. In contrast with control subjects, serum IL-6 levels did not display diurnal variations in stroke patients. In stroke patients, but not in controls, IL-6 level correlated significantly with cortisol level and morning serum IL-6 level independently predicted evening/night cortisol level. In conclusion, brain ischemia could stimulate IL-6 release in blood and in this way modulate hypothalamo-pituitary-adrenal axis.

6-(4-Benzylpiperazin-1-yl)benzodioxanes as selective ligands at cloned primate dopamine D(4) receptors.

A series of novel 6-(4-benzylpiperazin-1-yl)benzodioxanes were prepared and screened at selected dopamine receptor subtypes. 6-(4-[4-Chlorobenzyl]piperazin-1-yl)benzodioxane (2d) had high affinity and selectivity for the D(4) dopamine receptor subtype and was identified as a D(4) antagonist via its attenuation of dopamine-induced GTPgamma(35)S binding at the D(4) receptor.

Design and synthesis of [(2,3-dichlorophenyl)piperazin-1-yl]alkylfluorenylcarboxamides as novel ligands selective for the dopamine D3 receptor subtype.

The dopamine D3 receptor subtype has been recently targeted as a potential neurochemical modulator of the behavioral actions of psychomotor stimulants, such as cocaine. However, definitive behavioral investigations have been hampered by the lack of highly selective D3 agonists and antagonists. In an attempt to design a novel class of D3 ligands with which to study this receptor system, a series of chemically divergent compounds that possessed various structural features that exist within several classes of reputed D3 agents was screened and compared to the recently reported NGB 2904 (58b). On the basis of these results, a novel series of compounds was designed that included functional moieties that were required for high-affinity and selective binding to D3 receptors. All the compounds in this series included an aryl-substituted piperazine ring, a varying alkyl chain linker (C3-C5), and a terminal aryl amide. The compounds were synthesized and evaluated in vitro for binding in CHO cells transfected with human D2, D3, or D4 receptor cDNAs. D3 binding affinities ranged from K(i) = 1.4 to 1460 nM. The most potent analogue in this series, 51, demonstrated a D3/D2 selectivity of 64 and a D3/D4 selectivity of 1300. Structure-activity relationships for this class of ligands at D3 receptors will provide new leads toward the development of highly selective and potent molecular probes that will prove useful in the elucidation of the role D3 receptors play in the psychomotor stimulant and reinforcing properties of cocaine.

[Polish multicenter study on diabetes type I incidence in he age group 0-14 between 1998 and 1999]. / Wieloosrodkowe badania nad zapadalnoscia na cukrzyce typu 1 w grupie wiekowej 0-14 lat w Polsce w latach 1998-1999.

The increase in diabetes type 1 incidence observed in various centers in Poland and the need for a centralized study covering large population have resulted in the construction of a standardized registry of type 1 diabetes in 1998 within the Polish Multicenter Study in Diabetes Epidemiology. The aim of the study was to present the incidence rates of type 1 diabetes in the age group 0-14 in 7 distinct regions of Poland (Krakow, Wroclaw, Warsaw, Bialystok, Poznan, Rzeszow and Olsztyn centers) with over 30% of the Polish population at risk in 1998 and 1999. The data for the standardized registry were obtained prospectively from paediatric hospital wards and diabetes outpatient units. The incidence rates calculated in 1998 showed the highest value of 14.6 and 14.5/100,000 for Olsztyn and Warsaw, and the lowest (8.4/100,000) for Poznan center. In 1999 the highest value of 14.7/100,000 was noted in Krakow and the lowest (9.3/100,000) in Poznan center. The differences in diabetes type 1 incidence rates between age groups 0-4, 5-9 and 10-14 were found to be significant (p < 0.0005) and were also significant when incidence rates were compared between males and females in these age groups in the whole study area in 1998-1999 (p = 0.002 and p = 0.015 respectively).

[Polish multicenter study on type I diabetes incidence in the age group 15-29 between 1998 and 1999]. / Wieloosrodkowe badania nad zapadalnoscia na cukrzyce typu 1 w grupie wiekowej 15-29 lat w Polsce w latach 1998-1999.

The increase in diabetes type 1 incidence observed in various centers in Poland and the need for a centralized study covering a large population have resulted in the construction of a standardized registry of type 1 diabetes in 1998 within the Polish Multicenter Study in Diabetes Epidemiology. The aim of the study was to evaluate the incidence of type 1 diabetes in the age group 15-29 in 5 distinct regions of Poland (Krakow, Warsaw, Bialystok, Rzeszow and Olsztyn centers) with over 15% of the Polish population at risk in 1998 and 1999. The data for the standardized registry were obtained prospectively from hospital departments and diabetes outpatient units. The incidence rates calculated in 1998 showed the highest value of 11.2/100,000 for Krakow and its region, and the lowest (4.4/100,000) for Bialystok and its region. In 1999 the highest value of 12.3/100,000 was noted in Olsztyn and its region and the lowest (3.4/100,000) in Warsaw. There were significant differences in the incidence rates between the study centers were found. Incidence rates in the whole study area were significantly higher among males as compared with females in 1998 and 1999 (8.9/100,000 vs. 4.9/100,000; p = 0.0001), marked in the age groups 15-19 and 20-24 (p = 0.001 and p = 0.002 respectively). A significant increase in diabetes type 1 incidence (from 4.6/100,000 to 6.9/100,000) was found as compared with results of the "Three Cities Study" (1986-1988).

[Visual disability due to diabetes in Cracow voivodeship]. / Inwalidztwo wzroku spowodowane cukrzyca na terenie województwa krakowskiego.

Visual impairment and blindness are major complications of diabetes and are regarded as the most serious disability by most of patients. The purpose of the study was to determine the incidence and prevalence due to diabetes-induced visual disability in 1991-1999 in the former Cracow voivodeship with population of 1,245,047 inhabitants. A register of visual disability was established using independent sources of information. On the end of 1999 the register had included 122 diabetics with visual disability--66 women (54.1%) and 56 men (45.9%). The patients with type 2 diabetes predominated--92 subjects (75.4%). The remaining 30 patients (24.6%) had type 1 diabetes. Grade 1 visual disability was diagnosed in 82 subjects (67.2%) whereas grade 2 visual disability in 40 patients (32.8%). Grade 1 visual disability was defined as visual acuity in a better eye < 0.05 and visual field narrowing < 20%. The criteria of grade 2 were visual acuity after correction in a better eye 0.05-0.1 and visual field narrowing 20-30%. According to the register of the Cracow Branch of the Polish Association of the Blind diabetics made up 6.2% of all visual disability cases. In 1991-1999 the incidence of visual disability due to diabetes did not increase significantly. The mean incidence rate was 0.9/100,000 population. However, there was a significant increasing trend in prevalence with mean annual increase of 0.24/100,000 population (95% CI 0.17-0.31/100,000).

trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents.

The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for the D(2) and D(4) receptors in a ratio similar to that observed for the atypical neuroleptic clozapine. The compounds (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dichlorophenyl)piperazine (5m) and (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dimethylphenyl)piperazine (5t) were selected for functional antagonists at D(2) and D(4) receptors and had a D(2)/D(4) ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity.

Design, synthesis, and discovery of 3-piperazinyl-3,4-dihydro-2(1H)-quinolinone derivatives: a novel series of mixed dopamine D2/D4 receptor antagonists.

3-Piperazinyl-3,4-dihydro-2(1H)-quinolinone derivatives (delta-lactams) were designed, synthesized, and identified as a new series of mixed dopamine D2/D4 receptor antagonists. To further the structure-activity relationship (SAR) study, 3-piperazinylindolin-2-ones (gamma-lactams) and 3-piperazinyl-3H,4H,5H-benzo[f]azepin-2-ones (epsilon-lactams) were also prepared and examined.

A topographic analysis of atrophic gastritis and stomach cancer risk. A clinicoepidemiological study in Poland.

The purpose of this cross-sectional study was to assess the relation between intestinal and diffuse stomach cancer at its various locations with topography of atrophic gastritis. The study population consisted of 3435 patients who reported over the period of 1991-1994 for the first time to gastroenterological outpatient clinics of 7 university medical centers in Poland. Among these subjects there were 131 histologically proved consecutive cases of gastric carcinoma. The reference group consisted of 1540 patients among whom endoscopic examination did not reveal peptic ulcers, polyps, deformations of antrum or bulbus duodenum and mucosa erosions. Gastroscopy on gastric cancer patients and the reference group was performed and biopsy specimens were obtained from the tumour and from the antrum and stomach corpus distant from the tumour. Among the gastric cancer cases there was a higher prevalence of atrophic gastritis in the intestinal than in the diffuse type. The highest prevalence of atrophic gastritis irrespective of its degree and stomach area was observed in the tumour-area of intestinal cancer located distally (78.9%), and the lowest in the tumour-free area in diffuse proximal cancer (18.5%). Prevalence of atrophic pangastritis (atrophic gastritis present both in the corpus and antrum) was also highest in intestinal distal cancer (69.2%) and lowest in diffuse proximal cancer (21.7%). The age-adjusted correlation coefficients between gastritis score in the tumour-area and tumour-free area were highly significant. It was shown that only atrophic pangastritis was significantly associated with gastric cancer irrespective of its histology and location (OR = 3.8, 95% CI:2.4-6.0), however, it was much stronger related to the intestinal gastric cancer (OR = 5.9, 95% CI: 3.1-11.0), than to the diffuse carcinoma (OR = 2.2, 95% CI: 1.1-4.3).

A clinico-epidemiological study on gastritis in gastric carcinoma and in non-cancerous gastric pathology in Poland.

To investigate the risk of gastric cancer development in subjects with atrophic and nonatrophic gastritis, we studied 221 consecutive gastric cancer patients and 7647 non-cancer subjects for whom endoscopic biopsy of the gastric mucosa was available. In gastritis patients, the relative risk (RR) estimates of gastric cancer were as follows: corpus atrophic gastritis RR = 8.7 (95% CI = 5.4-14.1), antral atrophic gastritis RR = 4.5 (2.4-8.1), chronic atrophic pangastritis RR = 7.6 (3.8-15.3), corpus nonatrophic gastritis RR = 1.6 (0.9-2.7), antral non-atrophic gastritis RR = 1.2 (0.7-2.3), and pangastritis RR = 1.3 (0.6-2.8). The latter was of borderline significance (p = 0.07). In peptic ulcer, a significant excess risk was calculated for subjects with either corpus atrophic gastritis (RR = 3.1 [2.5-3.9] or antral atrophic gastritis (RR = 3.5 [2.6-4.8]). For stomach polyps, the risk was significantly increased only in subjects with corpus atrophic gastritis (RR = 2.1 [1.3-3.5]). The risks for both peptic ulcer and polyps, however, were significantly increased in chronic atrophic pangastritis. A substantial excess risk of gastric cancer was found for atrophy in the corpus (RR = 20.9 [9.0-48.9]) and in the antrum (RR = 14.9 [5.3-41.9]). An increased risk of peptic ulcer was also confirmed in subjects with atrophy in the corpus (RR = 3.0 [1.3-6.9]) and in the antrum (RR = 4.9 [2.0-12.1]).

[Program contents of undergraduate teaching of epidemiology to medical students and its evaluation]. / Zalozenla programowe nauczania przeddyplomowego epidemiologii w Collegium Medicum Uniwersytetu Jagiellonskiego wraz z jego ocena przez studentów.

The importance of epidemiology in modern medicine increased rapidly during the last years. Now each physician should know basic epidemiological definitions and epidemiological strategy for studies on health and disease. The course of epidemiology, as a separate subject for medical students, was introduced to curriculum of Medical Faculty in 1970. At present, the course covers 4 lecture units and 16 exercise units. It is conducted on 4th year of the Medical Faculty. The evaluation of the course carried out in 1995 showed that a great majority of medical students considers it as interesting and useful subject to be taught.

[Controlled clinical studies for topographic analysis of atrophic gastritis and stomach cancer]. / Badania kliniczno-kontrolne nad topografia zanikowego zapalenia blony sluzowej i rakiem zoladka.

The purpose of this cross-sectional study was to assess the relation between intestinal and diffuse stomach cancer at its various locations with topography of atrophic gastritis. The study population consisted of 3435 patients who reported over the period of 1991-94 for the first time to gastroenterological outpatient clinics of 7 university medical centers in Poland. Among these subjects there were 131 histologically proved consecutive cases of gastric carcinoma. The reference group consisted of 1540 patients among whom endoscopic examination did not reveal peptic ulcers, polyps, deformations of antrum or bulbus duodenum and mucosa erosions. Among the gastric cancer cases there was a higher prevalence of atrophic gastritis in the intestinal than in the diffuse type. The highest prevalence of atrophic gastritis irrespective of its degree and stomach area was observed in the tumour-area of intestinal cancer located distally (78.9%), and the lowest in the tumour-free area in diffuse proximal cancer (18.5%). Prevalence of atrophic pangastritis (atrophic gastritis present both in the corpus and antrum) was also highest in intestinal distal cancer (69.2%) and lowest in diffuse proximal cancer (21.7%). For other types of cancer the prevalence rates of atrophic pangastritis was 50.0% in intestinal proximal cancer and 37.5% in diffuse distal carcinoma. The age-adjusted correlation coefficients between gastritis score in the tumour-area and tumour-free area were highly significant. It was shown that only atrophic pangastritis was significantly associated with gastric cancer irrespective of its histology and location (OR = 3.8, 95% CI:2.4-6.0), however, it was much stronger related to the intestinal gastric cancer panga (OR = 5.9, 95% CI: 3.1-11.0), than to the diffuse carcinoma (OR = 2.2, 95% CI: 1.1-4.3).