Vinorelbine, epirubicin, and methotrexate (VEM) as primary treatment in locally advanced breast cancer.

PURPOSE: This phase II trial of VEM (vinorelbine + epirubicine + methotrexate) in the treatment of locally advanced breast cancer was conducted to obtain downstaging to allow surgery and breast conservation. PATIENTS AND METHODS: This multicenter study recruited 58 patients with locally advanced breast cancer (two patients ineligible); 56 were evaluable for response and tolerance. RESULTS: Downstaging was obtained in 77% of the patients with a pathological complete response (pCR) rate of 9%. At 33 months of follow-up, median survival has not been reached. Neutropenia grade 3-4 was reported in 31% of cycles with 3% of cycles with infection grade 3. Alopecia grade 3 was noticed for 71% of patients. CONCLUSION: VEM represents an effective regimen for patients with locally advanced breast cancer, allowing an important pCR. Moreover, this regimen appears to be particularly well tolerated.

Far-reaching consequences of high level air pollution on the developing immune system.

The town of Dimitrovgrad in Bulgaria has a highly industrialized region with a developing chemical industry, cement and asbestos-cement production, as well as energy production. For over four decades, the main ecological problem was air pollution, but after 1989 a great economic crisis led to an abrupt decline in the level of air pollutants. The aim of the present study was to investigate the present state of humoral immunity in teenage children from Dimitrovgrad who lived under conditions of massive air pollution during their intrauterine development and first few years of childhood. Immunoglobulins IgA, IgM, and IgG were measured in 106 clinically healthy children (average age 12.68 +/- 0.56 y) from 3 schools in Dimitrovgrad and in 41 control subjects (average age 12.35 +/- 0.22 y) from the town of Nova Mahala, an area lacking massive sources of air pollution. Immunoglobulin concentration was determined by turbidimetry using an Optima (KONE) chemical analyzer. The average IgA, IgM, and IgG levels in children from Dimitrovgrad did not differ significantly from those of the control group.

Changes in plasma levels of acute phase proteins in pancreatitis.

UNLABELLED: The objective of our study was to determine whether the changes in the plasma levels of C-reactive protein, haptoglobin, transferrin, and alpha 1-acid glycoprotein (orosomucoid) in acute pancreatitis patients examined on days 1, 3, 5, 7, 9, and 14 after their admission to hospital can be used to assess the course and determine the severity of the disease, and to discriminate edematous from necrotizing pancreatitis. The study included 18 patients with mild pancreatitis and 20 patients with severe pancreatitis. Pancreatitis was classified as mild or severe according to Ranson and the Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Acute phase proteins were determined using the immunoturbidometric assay. The C-reactive protein in the mild pancreatitis patients was six-fold higher at admission, then gradually increased for 5 days and started to drop. In the severe clinical forms of pancreatitis the C-reactive protein had significantly high values throughout the whole time of study retaining this high level to day 14; these elevated levels correlated with the persistent severe general state of the patients and the extent of necrosis in the pancreas. The changes in the haptoglobin and transferrin levels were not significant. Orosomucoid level in mild pancreatitis cases remained constant whereas it was elevated and continuously above the reference values in severe pancreatitis. IN CONCLUSION: C-reactive protein level changes significantly in patients with acute pancreatitis; it is in the range of 100-120 mg/l in the mild forms of the disease and between 120 and 360 mg/l in the severe pancreatitis. This renders it a valuable indicator for the discrimination of edematous from necrotizing acute pancreatitis.

[The diagnostic value of changes in the kallikrein-kinin system indices in patients with acute pancreatitis]. / Vurkhu diagnostichnata stoinost na promenite na pokazatelite na kalikrein-kininovata sistema pri bolni s ostur pankreatit.

It is the purpose of the work to assay retrospectively the diagnostic value of KKS indicators--PK, KG, alpha 1-AT; alpha 2-MG, KOP N and plasminogen in the blood--studied in dynamics at 1, 3, 5, 7, 9 and 14 days after admission. For the purpose the percentage of patients showing abnormal values of the total number of cases being examined, with certain diagnosis acute pancreatitis and severity of the clinical form, is calculated. The highest is the rate of abnormal values for PK, next ranking KG, alpha 1-AT, KOP N and plasminogen the least. Presumably, PK and KG are adequate markers accurately mirroring the essence and dynamic pattern of the pathological process in acute pancreatitis patients.

[Changes in some of the kallikrein-kinin system indices in patients with acute pancreatitis]. / Promiana na niakoi ot pokazatelite na kalikrein-kininovata sistema pri bolni s ostur pankreatit.

Proceeding from the major role played by kinins in the pathophysiology of endogenic intoxication among acute pancreatitis patients (AP), and the conflicting and scarce literature data on the issue, the changes in the level of prekallikrein, high-molecular kininogen, alpha 2-macroglobulin, alpha 1-antitrypsin, plasminogen and carboxypeptidase N in the blood are studied in dynamics at 1, 3, 5, 7, 9 and 14 days after admission of 48 patients with mild, and 121 with severe form of acute pancreatitis. Forty-eight individuals are used for control purpose. PK, KG and plasminogen are assayed using the colorimetric method of the Boehringer Company--Mannheim, KG--by chronometric test of the Sigma Diagnostics Company, CPO N--after Folk's method, as modified by Erdös, alpha 2-MG--by radial immunodiffusion according to Mancini, and alpha 1-AJ--by immunoturbidometric method. As shown by the results, in acute pancreatitis KKS activation occurs, demonstrated by the reduced PK, KG and alpha 2-MG values, and by the statistically significant enhancement of alpha 1-DJ, COP N and plasminogen activity. In patients presenting mild forms the aforementioned changes are rather weakly manifested and transient, while in the serious forms they are markedly expressed and persisting. In either form the deviations are rather pronounced in the first three days of disease. Coinciding with a clinical course characterized by cardiovascular changes similarly strongly manifested.

[Changes in the concentration of individual proteins in women using current peroral contraceptives]. / Promeni v kontsentratsiiata na individualnite beltutsi pri zheni, upotrebiavashti suvremenni peroralni kontratseptivi.

UNLABELLED: BUT: The aim of the present study was to establish the influence of the moderate combined oral contraceptives on the concentration of the individual proteins in serum. MATERIAL AND METHODS: The study included 70 women at the age from 16 to 30, separated into two groups: control group, including 30 women who have not used OC basic group, including 40 women using Cilest and Marvelon in the period of one to three years. There have been examined the following individual proteins in serum: prealbumin; orosomucoid; haptoglobin; TRA; C3; C4; CRP; IgA; IgG and IgM. Their level in serum was defined with immunoturbidimetric method with monoclonal antibodies of the firm Kone (Fin). RESULTS: The data showed reduced concentrations of Orosomucoid and increased concentrations of TRA in the basic group. CONCLUSIONS: The continuous use of Cilest and Marvelon do not influence the concentrations of the examined individual proteins in the serum. They lead to reduced concentrations of orosomucoid and increased concentrations of TRA.

Effect of pectin on some electrolytes and trace elements in patients with hyperlipoproteinemia.

BACKGROUND: Water-soluble dietary fibres are widely used in preventive and curative nutrition, especially in cases of hyperlipoproteinemia. Occurrence of disturbances of the electrolyte and trace element metabolism causing adverse effects in long-term treatment with pectin can be theoretically substantiated. METHODS: Seventy three patients with hyperlipoproteinemia, aged from 40 to 69 years, were included in the study. They were treated with a natural product, based on high-esterified pectin granulated with sorbitol. The patients were examined prior to the treatment and once monthly during the three-month course of therapy. RESULTS: The results of the comparative assessment of the electrolytes (sodium, potassium, chloride, ionised calcium, total and ionised magnesium) failed to reach statistical significance during the administration of the pectin product. Neither did the serum level of trace elements (iron and copper) change significantly during the observed period. CONCLUSIONS: The biochemical analysis of the serum level of certain electrolytes and trace elements indicate that daily administration of 15 g of high-esterified apple pectin for a three-month period has no adverse effects. Therefore pectin products can be included in the therapeutic schedule in the treatment of hyperlipoproteinemia.

Evaluation of an ion-selective electrolyte analyzer: Microlyte 6.

Microlyte 6 (Kone, Finland) is an ion-selective analyzer designed to measure simultaneously the concentration of six important electrolyte parameters--potassium, sodium, chloride, ionized calcium, ionized magnesium and pH in whole blood, serum and plasma. Two values are obtained in analyzing the ionized fractions of magnesium and calcium--one at the actual pH and another at a recalculated measurement for pH = 7.4. Direct determination of ionized calcium and ionized magnesium simultaneously with that of the other electrolytes is of great clinical significance. It is only recently that ion-selective analysis of ionized magnesium has been proposed. The analytical reliability of the results and the operational characteristics of the Microlyte 6 ion-selective analyzer were evaluated for approximately one year. The coefficient of variation of the results in the reference and pathological range was 0.49%-2.23%, and 0.68%-4.42% for the within-run and between-run series, respectively. The inaccuracy of the results expressed by d% was from -4.23% to +4.06%. The comparative evaluation of the results for potassium, sodium, chloride, and ionized calcium between Microlyte-6 and the clinical chemistry analyzer Dynamic (Kone) showed a high correlation (correlation coefficient in the range 0.9868-0.9970). The correlation between the results for the ionized fraction and those obtained for total magnesium was consistent with that generally given in the literature.

Apometallothionein in rat liver.

The identification of apometallothionein (AMT) in rat liver by reversed-phase high-performance liquid chromatography (RP-HPLC) after gel permeation was realized in experiments performed both in vivo and in vitro. The reliable assignment of the corresponding AMT peak permitted the detection and determination of AMT in different groups of experimental and control rats. In all animals studied (more than 100 rats), AMT was always present in amounts higher than that of metallothionein (MT) or compatible with it. Induction of MT synthesis by CdCl2 subcutaneous injections decreased the AMT level and increased the MT level, but nevertheless the amount of AMT still remained relatively high.

Metallothioneins in spontaneously hypertensive rat liver.

The metallothionein (MT) synthesis was induced in the liver of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats through sc injections of CdCl2 for 3 and 6 days. The MT contents of the liver of these animals and of untreated rats from both groups were determined by gel filtration, HPLC, SDS/PAGE and amino acid analysis. The isoforms MT1 and MT2 were identified and their Cd, Zn and SH-group contents were determined. The SHR showed significantly higher values of MT than WKY rats in the untreated animals and on the 3rd day of the induction. On the 6th day, the MT levels in both groups were equal. The Cd and Zn contents followed the MT concentration in the homogenates. The possible relation between the arterial hypertension and the zinc and copper homeostasis is discussed.

Opiate receptor binding in the brain of rat during stress.

Two types of opioid receptors were studied in the brain of rats: Delta (for endogenous opiate) and mu (for exogenous opiates). 3H derivates: D-Ala2-enkephalin and Naloxone were used as labeled ligands. The results obtained were calculated by computer program for automatic estimation of the data using approximation equations. An increase of binding delta receptors is observed in both types of stress (2-8 times), while to the mu receptors the binding is less effective mainly after irradiation. These data suggest that a close interaction exists between sympathoadrenal system and opioid mechanisms during stress.

Discrepancy between aldosterone production and renin-angiotensin system activity in Brattleboro rats.

It was demonstrated before that in addition to their typical changes in water-sodium-potassium balance Brattleboro rats, homozygous for hypothalamic diabetes insipidus (DI), revealed a discrepancy between aldosterone level and plasma renin activity (PRA). In the present study PRA was significantly increased (79%), and concomitantly juxtaglomerular (JG) index was increased, reflecting an increased secretory activity of renin-producing JG cells. Plasma concentration of aldosterone was significantly lower (-36%) in DI rats than in their Long Evans (LE) controls. Adrenal blood flow rates were not significantly different in both groups of rats but aldosterone concentrations in the adrenal venous effluents were significantly lower (-66%) in DI rats than in LE rats, suggesting that in vivo production rate of aldosterone was reduced in DI rats. This assumption was confirmed by morphometric data of zona glomerulosa. Our results demonstrated a significant reduction (50%) of angiotensin II receptors in the adrenal glands of DI rats, referring to the number of binding sites and to Kd. This finding threw light on the dissociation between a decreased aldosterone production and stimulated renin-angiotensin system in DI rats.

Angiotensin II receptors in the brain and adrenal glands of rats with experimental and spontaneous hypertension.

Angiotensin II receptors in the brain and adrenal glands of rats with experimental and spontaneous hypertension were studied. The data have shown that the capacity of binding sites does not change substantially in the adrenal gland while in the brain of spontaneous hypertensive rats it is lower and increases in those with experimental hypertension. There is also a change in the affinity of binding in both the adrenal gland and the brain of the spontaneously hypertensive rats. The data suggest some changes in tissue sensitivity to hormone in the spontaneously hypertensive rats.

Content of prostaglandins E and F in the blood plasma and kidneys in arterial hypertension (clinical-experimental study).

A dynamic study is made of the content of PGE and PGF2 alpha in the kidneys of rats with experimental coarctation hypertension, as well as the PGF2 alpha-metabolite in the blood plasma of the same experimental model in rats and in patients with arterial hypertension. The level of the PGF2 alpha-metabolite tends to decrease both in the animals with experimental hypertension and in hypertonic patients. In rats with 30-day hypertension low values are established in 55 per cent, while in 45 per cent there are high values of the PGE level in the kidney homogenate compared with the control group. The concentration of PGF2 alpha in the left ("endocrine") kidney (whose artery originates distally from the place of aortic coarctation) is higher than the concentration of the same PG in the right kidney. Our findings give grounds for the following assumptions: 1. The PGF2 alpha-metabolite as hormone and partly PGE in the kidneys seem to be involved in the pathogenesis of arterial hypertension as compensatory factors. 2. PGF2 alpha in the kidneys probably participates directly as one of the elements of the complex pathogenesis of arterial hypertension.