Soluble P-selectin glycoprotein ligand - a possible new target in ulcerative colitis.

BACKGROUND: The main characteristic of active inflammatory bowel disease (IBD) is the neutrophil infiltration into the intestinal lamina propria, where neutrophils usually do not reside. Selectins are cell surface glycoproteins responsible for binding the leukocytes to vascular cells and their extravasation into the surrounding tissue. They show high affinity to P-selectin glycoprotein ligand-1 (PSGL-1) receptors. PSGL-1 is expressed on the surface of all leukocytes and they mediate the rolling of neutrophils on P-selectin. Soluble PSGL-1 acts competitively with cellular PSGL in many physiological and pathological processes.The aim of our study was to compare serum sPSGL-1 concentration in the blood of patients with ulcerative colitis (UC) and healthy control subjects. METHODS: Serum concentrations of sPSGL-1 were measured in 20 patients with UC and 20 control subjects. Two-layer immunoenzyme procedure (ELISA) was used. RESULTS: The mean (± standard deviation) serum concentrations of sPSGL-1 in patients with UC and controls were 349.97±75.40 U/mL and 284.39±52.40 U/mL, respectively (p=0.003). CONCLUSION: In the present study, we showed that patients with UC had significantly higher sPSGL-1 blood values in comparison with healthy subjects. A short-term blockade with anti-PSGL-1 antibodies could block the transport of neutrophils and decrease UC activity. Thus it could possibly be employed in a new therapeutic approach to the treatment of UC (Fig. 1, Ref. 25).

Liver angiosarcoma and hemangiopericytoma after occupational exposure to vinyl chloride monomer.

Various malignant tumors of the liver, especially liver angiosarcoma, have been described after occupational exposure to vinyl chloride monomer. We present the case records and pathologic findings of two plastic industry workers who had been exposed to high concentrations of vinyl chloride. These workers developed hepatic neoplasms, angiosarcoma, or hemangiopericytoma. We discuss the histogenesis of these tumors; the common vascular origin and the mutual transformation of these two tumors suggest that the hemangiopericytoma may also have developed during occupational exposure to high concentrations of vinyl chloride monomer.

Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in hypertensive patients.

A double-blind clinical trial was conducted to compare the efficacy of and electrolyte changes caused by ramipril-chlorthalidone combination treatment (5 mg + 25 mg) and chlorthalidone monotherapy (25 mg daily) in patients with hypertension. After a 4-week placebo period, 32 patients (mean age, 51 +/- 9 years) with essential hypertension (average blood pressure of 181.4/104.5 +/- 13.0/6.9 mmHg) were randomly assigned to receive combination therapy (group A, n = 17) or monotherapy (group B, n = 15). After 12 weeks of active treatment, systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively, for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for patients taking monotherapy. The difference was significant for between-group comparisons. There were no changes in serum sodium concentration, but a significant similar increase in 24-hour urinary sodium excretion was seen in both groups. Serum calcium levels increased slightly and 24-hour urinary calcium excretion decreased significantly in both groups, probably due to chlorthalidone administration. Serum potassium levels increased slightly in group A (from 4.16 +/- 0.39 mmol/L to 4.30 +/- 0.42 mmol/L) and decreased slightly in group B (from 4.18 +/- 0.32 mmol/L to 3.99 +/- 0.49 mmol/L). Urinary potassium excretion did not change significantly in group A, but increased by approximately 15% in group B. There was a decrease in 24-hour urinary magnesium excretion (from 4.01 +/- 1.24 mmol/24 hours to 3.50 +/- 0.93 mmol/24 hours) in group A and an increase (from 3.49 +/- 0.98 mmol/24 hours to 4.35 +/- 1.12 mmol/24 hours) in group B. At the end of the trial these changes were significant in between-group comparisons. Consistent with the previously shown amelioration by ramipril of thiazide-induced metabolic side-effects, ramipril appears to improve magnesium balance during cotreatment with chlorthalidone.

[The effect of hemoglobin levels in the blood in pulmonary diffusing capacity]. / Utjecaj koncentracije hemoglobina u krvi na difuzijski kapacitet pluca.

Using a "single breath" method, diffusing lung capacity (DLCO) and unit DLCO (KCO) were measured in 19 patients with chronic sideropenic anemia and 19 healthy women who were without any clinical or radiologic evidence suggestive of cardiorespiratory disease. Anemic patients, compared to the control group, had significantly reduced DLCO (% predicted) and KCO (% predicted) (p < 0.01). Each 10 g/L hemoglobin (Hb) reduction below a normal value of 136 g/L corresponded to 2% DLCO% and 3% KCO% reductions. For all examinees, where the range of Hb was from 50 to 150 g/L, a significant positive low linear correlation was noted between DLCO% and HB (r = 0.31; p = 0.049) and KCO% and Hb (r = 0.43; p = 0.005). Analyzing only anemic patients, where the range of Hb was from 50 to 109 g/L, no significant correlation was found between Hb and DLCO% or KCO%. Therefore, in patients with chronic sideropenic anemia DLCO is lowered less then expected, so one should not adjust measured DLCO or KCO values to standard Hb concentration, because probably various pathophysiological compensatory mechanisms affect DLCO components in unknown manner, changing the relationship between Hb and DLCO.

Q-T interval as predictor of serum calcium level.

To assess whether measurement of the electrocardiograhic (ECG) Q-T interval is a useful predictor of total serum calcium concentration, 15 uraemic patients were studied (10 female, five male; age range, 25-60 years). Resting ECGs were interpreted by three independent observers without knowledge of the patients' identity or serum calcium. Three variants of measurement of the Q-T interval were analysed, of which Q-aTc, the interval from the beginning of the Q-wave to the apex of the T-wave, was the most consistent (coefficient of variation, 2.7%). This also provided the best correlation with measured serum calcium concentration (P < 0.001). When compared to biochemical measurements, the predicted serum calcium concentration was within 95% confidence limits in 14 of the 15 patients studied. However, the wide confidence limits of this technique mean that it cannot be recommended in routine clinical practice.

[Comparison of amlodipine and the nifedipine retard preparation in the treatment of arterial hypertension]. / Usporedba amlodipina i retard pripravaka nifedipina u lijecenju arterijske hipertenzije.

The efficacy and acceptability of amlodipine (5-10 mg o.d.) and sustained-release nifedipine (20-40 mg b.i.d.) were compared in a multicenter, double-blind clinical trial. After a two-week placebo period, 71 essential hypertensives of both sexes, aged 51.7 +/- 8.5 years, having diastolic blood pressure of 95-114 mmHg were randomly allocated to either amlodipine 5 mg once daily (group A) or nifedipine 20 mg twice daily (group B). With respect to the blood pressure response, the initial dose was doubled after two weeks. No significant differences in blood pressures recorded at baseline and at the end of the placebo period were demonstrated. A significant reduction in both systolic and diastolic blood pressures in the supine position was observed already two days after the start of treatment. In the group A it decreased from 163.2 +/- 21.4/102.7 +/- 8.5 to 155.7 +/- 20.7/98.2 +/- 8.9 mm Hg (p < 0.05) and in the group B from 160.5 +/- 16.2/100.5 +/- 12.2 to 152.2 +/- 17.0/95.4 +/- 9.5 mm Hg (p < 0.05). The similar changes of blood pressure were observed in the standing position, as well. At the end of the study, the overall reduction of the supine diastolic blood pressure was 12.5% in the group A versus 5.2% in the group B (p < 0.05). In the standing position, amlodipine decreased diastolic blood pressure by 8.8% and nifedipine by 6.4% (p < 0.05). Furthermore, amlodipine decreased the standing diastolic blood pressure to a greater extent (8.8% versus 6.4%; p < 0.05) than nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

[Orthostatic hypotension. Case report of the Bradbury-Eggleston syndrome]. / Ortostatska hipotenzija. Prikaz slucaja Bradbury-Egglestonova sindroma.

A case of a 71-year-old woman with idiopathic orthostatic hypotension is presented. Several diagnostic procedures which can detect sympathetic pathway lesion are reported. The value of blood pressure measurement and heart rate response to the supine and standing position deep breath, Valsalva maneuver and cold pressor test in differential diagnosis are emphasized. The venoconstriction, venous reflexes and tyramine tests are described, as well. The authors favour an individual therapeutic approach with no limitation of mineralocorticoid dosage. Nonpharmacological measures, such as an increased salt intake, elastic support stockings and swimming are highly recommended.

[Magnesium--pathophysiology and clinical aspects]. / Magnezij--patofiziologija i klinika.

Magnesium is one of the most wide-spread elements in nature. It is the fourth major cation in the human body (after Ca, Na and K), and the second most abundant within the cells (after K). More than 300 enzymatic reactions depend on the presence of magnesium, especially concerning the generation and use of adenosine triphosphate. Magnesium level is controlled by the kidneys and gastrointestinal tract. It appears closely linked to calcium, potassium and sodium balance. The fundamental role played by magnesium in different biological systems has been recognized during recent years, and disorders of magnesium metabolism are now diagnosed and treated more often. There are several molecular and cellular actions of magnesium that explain clinical manifestations of magnesium deficiency or excess. Treatment of altered magnesium status depends on the clinical setting. Guidelines for therapy are given.

[How much do we understand about pharmacotherapy of cardiac arrhythmias?]. / Koliko razumijemo farmakoterapiju srcanih aritmija?

By an anonymous, multiple-choice questionnaire assessed was the knowledge of cardiac electrophysiology and mechanism of action of some antiarrhythmic drugs among the staff members of a department of medicine from a large regional hospital. The overall results were disappointing (over 55 per cent of inaccurate answers), but improved after 3 months (less than 30 per cent). It is concluded that such a polling increases the level of awareness about target problem (cardiac arrhythmia management in the actual case) and improves the performance of health professionals.

[Does one-fifth of our population really die from smoking?]. / Umire li zaista petina naseg pucanstva zbog pusenja?

Scientific research has confined the causal connection between tobacco smoking, i. e. inhaling of tobacco smoke and malignant and other disease. As reported by WHO experts, tobacco smoke is one of the main causes of death from lung cancer in 90-95% cases, in other types of cancer in 45-50%, lung obstructive diseases, chronic bronchitis and emphysema in 75-80% and cardiovascular diseases in 20-25%. According to the above given percentage, in the Republic of Croatia average of over 10,000 persons die yearly as a consequence of tobacco smoking out of which 3,000 on the territory of Zagreb, or 20% of the total number of dead. The Committee for deliberating Zagreb from smoking has initiated the intersection approach to the control of smoking as a part of the "Healthy City" Movement. As a conclusion, all health institutions and professional associations of health workers are called to make public assessment of the harm smoking can do to the health of our citizens and take necessary legal measures for its control.

[Outpatient approach to arterial hypertension: analysis of ambulatory care of hypertonic patients at the Clinical Hospital Center in Split 1988-1990]. / Izvanbolnicki pristup arterijskoj hipertenziji: analiza rada ambulante za hipertonicare KBC Split 1988-1990.

A retrospective analysis of 5,088 hypertensives treated by our Outpatient Clinic, Department of Medicine, University Hospital Split from 1988 through 1990 is presented. Male sex was predominant (about 65%) and almost all the patients (over 95%) were overweight and the majority (over 50%) have had mild hypertension. Essential form was by far the most prevalent type of hypertension (over 95%), while curable forms of secondary hypertension were rare indeed (less than 0.2%). Diuretics and beta blockers, the traditional first-line antihypertensives were the most prescribed drugs (over 60%), while the share of ACE inhibitors, calcium antagonists and alpha blockers was steadily increasing. General measures, such as body weight reduction, salt restriction or cessation of smoking, although obligatory part of the treatment and suggested to each hypertensive, are rarely carried out.

Controlled multicentre comparison of captopril versus lisinopril in the treatment of mild-to-moderate arterial hypertension.

The antihypertensive efficacy and safety of lisinopril (L), a novel ACE inhibitor, were compared to those of captopril (C), the familiar drug of the same class, in a multicentre controlled trial. The study included 91 mild-to-moderate, middle-aged hypertensives of both genders, 46 of which were randomized to C and 45 to L. After a two-week placebo period the examinees were receiving either L o.d. in increasing dosage of 10, 20, or 40 mg per day (amount necessary to achieve normotension), or C b.i.d. in a corresponding daily dose of 25, 50, or 100 mg. During the eight-week formal part of the trial, L decreased the systolic blood pressure from the initial values by an average of 14.9%, and the diastolic pressure by some 15.2%. The same parameters were lowered on C by 11.2%, and 11.7%, respectively. The mean arterial pressure from an initial average of 125.5 mmHg was lowered to 110.9 mmHg on C (11.6% reduction, p < 0.01), and from 125.3 mmHg to 108.2 mmHg on L (13.6% reduction, p < 0.01). Although the L effects were more pronounced, the observed between-group differences did not reach the level of statistical significance, except for the achievement of normotension, which disclosed the superiority of L (p < 0.05). The tolerability of both drugs was good and only one examinee had to be excluded because of side-effects (proteinuria). It is concluded that both ACEIs under study showed comparable efficacy and safety, L being marginally more potent and longer acting.

[Comparison of captopril and lisinopril in the treatment of mild and moderate hypertension]. / Usporedba kaptoprila i lizinoprila u lijecenju blage i umjerene arterijske hipertenzije.

The antihypertensive efficacy and safety of lisinopril (L), a novel ACE inhibitor, was compared to captopril (C), the known and already approved drug in our country in a multicenter double-blind Yugoslav trial. The study included 91 mild-to-moderate hypertensive patients of both sexes. Forty-six patients were randomized to receive captopril and 45 lisinopril. After a 2 week placebo, the examinees were administered either L in increasing dose of 10, 20, or 40 mg per day (amount necessary to achieve normotension), or C in a dosage of 25, 50, or 100 mg per day. During the 8 week formal trial L decreased the systolic blood pressure by an average of 14.9% from the initial values, and the diastolic pressure by some 15.2%. The same parameters were lowered on C by 11.2%, and 11.7%, respectively. Although the L effects were more pronounced, the observed differences did not reach the level of statistical significance (except for the dose-to-normotension relationship which was significantly better in the L group). It is concluded that both ACEIs under study showed comparable efficacy and tolerability, L being marginally more potent, and longer acting.

[Parameters significant for the prognosis of chronic myeloid leukemia in the chronic phase]. / Istrazivanje parametara znacajnih za prognozu kronicne mijeloicne leukemije u kronicnoj fazi.

A total of 46 patients with chronic myeloid leukaemia and their clinical and laboratory findings as parameters which might have an influence on survival were investigated. There was 28 (61%) males and 18 (39%) females. The mean age was 52 years. The patients were treated by busulfan with daily doses of 6 to 10 mg during one to two months, following the treatment by the lower doses of busulfan. A complete remission was achieved in 40 (87%) patients, in 4 (9%) there was a partial remission, and in 2 (4%) no remission at all. The median duration of chronic phase was 36 months, and the median survival for all patients was 43 months. The females survived longer than the males, but there was no significant difference in the survival time (median 46:38 months). The patient's age did not appear to influence prognosis. No differences in survival was noted between the patients with the haemoglobin level higher or lower than 110 g/L (chi 2 = 1.64). The size of the spleen was not a factor of statistical significance for the patients analysed. In patients with leukocytosis higher than 100 x 10(9)/L and those with more than 6% basophils in the bone-marrow smears, the survival was worse than in patients with the finding below this value (chi 2 = 3.55; 3.87). In the group of patients with platelet count higher than 350 x 10(9)/L, the survival was significantly worse than in patients with the finding below this value (chi 2 = 4.67; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)