Acute effects of monounsaturated fat on postprandial lipemia and gene expression in first-degree relatives of subjects with type 2 diabetes.

BACKGROUND/OBJECTIVES: Subjects with type 2 diabetes (T2D) and their nondiabetic first-degree relatives (REL) have increased risk of cardiovascular disease (CVD). Postprandial triglyceridemia (PPL), influenced by diet, is an independent risk factor for CVD. Dietary fat elicits increased PPL in T2D compared with nondiabetic controls, but our knowledge of PPL responses to fat in REL is sparse. Our aim was to test the hypothesis that REL respond to a monounsaturated fatty acid (MUFA) challenge with a higher PPL response compared with controls who have no family history of T2D (CON) and that MUFAs exert a differential impact on incretin responses and on the expression of genes involved in carbohydrate and lipid metabolism in muscle and adipose tissues of REL and CON. SUBJECTS/METHODS: A total of 17 REL and 17 CON consumed a meal with 72 energy percent derived from MUFAs (macadamia nut oil). Plasma triglycerides, free fatty acids, insulin, glucose, glucagon-like peptide 1, glucose-dependent insulintropic peptide and ghrelin were measured at baseline and regular intervals until 4 h postprandially. Muscle and adipose tissue biopsies were collected at baseline and at 210 min after the meal. RESULTS: The MUFA-rich meal did not elicit different responses (P>0.05) in PPL, insulin, glucose, incretins or ghrelin in REL and CON. Several genes were differentially regulated in muscle and adipose tissues of REL and CON. CONCLUSIONS: A MUFA-rich meal elicits similar PPL, insulin and incretin responses in REL and CON. MUFAs have a differential impact on gene expression in muscle and adipose tissues in a pattern pointing toward early defects in lipid metabolism in REL.

Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.

AIMS: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. FUNDING: Novo Nordisk A/S. RESULTS: After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p < 0.0001) significantly decreased with liraglutide 1.8 mg versus placebo, as did iAUC(0-8h) and C(max) (p < 0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. CONCLUSIONS: Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia.

Alcohol and type 2 diabetes. A review.

AIMS: To describe a) the association between alcohol consumption and the risk of type 2 diabetes (T2D) and b) the impact of alcohol on the glycemic control with and without anti-diabetic drugs. DATA SYNTHESIS: We searched MEDLINE and the Cochrane Library data base with the key words "Diabetes Mellitus, type 2" and "Alcohol Drinking" in English-language studies in adults. For the first part of the review we selected meta-analyses, review articles and observational studies more recent than year 1990 including at least 1000 participants. For the second part of the review we included all articles more recent than year 1990. Most observational studies find a J-shaped association between alcohol intake and incidence of T2D. Interestingly, drinking pattern plays a role, i.e. binge drinking increases the risk of T2D. Opposing information exists about the influence of beverage type. In T2D the acute effects on plasma glucose, insulin, fatty acids and triglyceride vary, in part depending on concomitant intake of food. Acute alcohol intake does not induce hypoglycemia in diet treated T2D, but increases the risk of hypoglycemia in sulphonylurea treated patients. In most studies, long-term alcohol use is associated with improved glycemic control in T2D. CONCLUSIONS: Alcohol consumption reduces the incidence of T2D, however, binge drinking seems to increase the incidence. Acute intake of alcohol does not increase risk of hypoglycemia in diet treated subjects with T2D, only when sulphonylurea is co-administered. Long-term alcohol use seems to be associated with improved glycemic control in T2D probably due to improved insulin sensitivity.

Preliminary results of mitomycin C local application as post-treatment prevention of vaginal radiation-induced morbidity in women with cervical cancer.

PURPOSE: To determine the usefulness of local mitomycin C application in the prophylaxis of vaginal narrowing after irradiation. MATERIAL AND METHODS: 31 patients with advanced cervical cancer qualified for the study. They underwent brachytherapy with iridium-192 isotope and external beam therapy with linear accelerators. In a blind probe method 16 patients were chosen to have an aqueous solution of mitomycin C applied to the vagina. RESULTS: Radiotherapy caused a shortening of vaginal length in both groups (study and control). In the "mitomycin C group" complete vaginal occlusion was visibly less frequent as were solid fibrotic vault changes. CONCLUSIONS: This mode of morbidity prevention can potentially diminish the occurrence of local vaginal fibrosis and thus may improve patients' quality of life. Further investigations are needed to confirm these results.

Preoperative brachytherapy in endometrial cancer--proposal of a new clinical protocol.

High-dose rate brachytherapy preoperative treatment has been described. The proposal of a protocol contains an outline of patient qualifications for this kind of treatment, as well as necessary laboratory and diagnostic imaging examinations. Methods of brachytherapy (low-dose rate and high-dose rate), methods of surgery and postoperative management of patients with endometrial cancer are discussed.

Small cell lung cancer I--III A: cytoreductive chemotherapy followed by resection with continuation of chemotherapy.

OBJECTIVES: To define the place for surgery in combined modality treatment of small cell lung cancer patients. The endpoint was: does complete resection reduce the risk of local failure? METHODS: Between November 1981 and June 1996, 75 patients in stage I--III A, many of them with a bulky cN2 tumor at presentation, were exposed to VP-16 based cytoreductive chemotherapy. After three courses of induction treatment, 46 patients underwent thoracotomy and 35 of them had resection. RESULTS: There were two sudden deaths (pulmonary embolism). No other complications were observed. In six cases (6/35 = 16%), no residual tumor was found in the resected specimen. Four weeks after surgery, chemotherapy was resumed. Three patients experienced local relapse (3/33), among them, the single patient with incomplete resection, and two other patients developed local and distant failure (2/33). Thus, the local relapse rate was 15% (5/33). Eight patients, mainly with chemotherapy induced surgicopathological complete remission (pCR) and with lymph nodes free of tumor in surgical specimens (pN0), are alive, tumor-free, at a median of 136 + months. Two patients died tumor-free at 65 and 147 months. One patient died of unrelated causes at 21 months with no evidence of disease at autopsy. The median survival in the cN0 + N1 subsets was 25.09 months, whereas in cN2 disease, this was 13.75 months. There were no long-term survivors among the patients with persistent N2 disease. The median survival in all 35 patients using the Kaplan--Meier method was 18 months; the 5-year tumor-free survival rate was 29% and the 10-year tumor-free survival rate was 23%. CONCLUSIONS: Satisfactory local tumor control confirmed the assumption of the study. No residual tumor in the resected specimen (pCR) is the most favorable prognostic factor and determinant of long-term survival. Surgery should not be performed in the patients with persistent N2 disease.

[The role of preoperative brachytherapy in the treatment of early invasive cervical cancer]. / Rola brachyterapii przedoperacyjnej w leczeniu wczesnych postaci inwazyjnego raka szyjki macicy.

The role of preoperative brachytherapy in the treatment of cervical cancer are discussed. Authors described a group of 45 patients with preliminary diagnosis of Io and IIo A sec FIGO tumour. Qualification system to combined treatment and diagnostic procedure are described. Authors discussed methods of LDR therapy. Tubes of 226Ra in Paris technique and afterloading 137Cs Selectron LDR/MDR (of Nucletron BV) were used. Postoperative histopathologic results are compared to preoperative diagnoses established on the basis of clinical examination, US and MRI. Preliminary assessment of tolerance and efficacy of these methods of treatment is made.

[Conservative and surgical treatment of pericarditis--our experience]. / Leczenie zachowawcze i zabiegowe zapalenia osierdzia--doswiadczenia wlasne.

Methods and results of both conservative and invasive therapy of pericarditis were analysed in the group of 30 patients. An emphasis was on successful treatment of mild (idiopathic) pericarditis and efficiency of the early started, combined pharmacotherapy (tuberculostatics + corticosteroids) of pericarditis of tuberculous etiology. A stress is on marked immediate efficacy of surgery in case of cardiac tamponade, independent on its etiology, with simultaneous recommendation of ultrasound-guided pericardial sac paracentesis. Survival rate in patients with malignant pericarditis is relatively low.

[Elective (prophylactic) brain irradiation in small cell lung cancer patients treated with chemotherapy combined with surgery]. / Elektywne (profilaktyczne) napromienianie mózgu u chorych na drobnokomórkowego raka pluca leczonych chemicznie w skojarzeniu z chirurgia.

The incidence of brain metastases in small cell lung cancer patients in the group without prophylactic cranial irradiation (PCI) was compared with the incidence of brain secondaries after PCI. Out of 29 patients without brain irradiation 13 patients experienced brain metastases at 19 months (13/29). On the contrary, no one out of 17 patients who received PCI was found to have brain metastases at 4 years. The justification of prophylactic cranial irradiation is presented and criteria of patients selection are given. Elective brain irradiation is indicated exclusively in patients with "limited disease" achieving complete response.

[Identification of a limited form of small cell lung cancer among 103 patients pre-selected for chemotherapy combined with surgery]. / Wyodrebnienie postaci ograniczonej drobnokomórkowego raka pluca w grupie 103 chorych wstepnie wyselekcjonowanych do chemioterapii w skojarzeniu z chirurgia.

Between Nov. 1981 and Nov. 1987 103 patients preselected for chemotherapy combined with surgery, therefore with local extension within homolateral mediastinal lymph nodes, with no signs of remote metastases, PS greater than or equal to 70, with no contraindication for resectional surgery including pneumonectomy, no diabetes, no prior treatment underwent first staging. Staging included: case history, physical examination, full blood count, biochemical tests (alkaline phosphatase, SGOT, GGTP, LDH), CEA, X-ray assessment including CT scan of the chest, bronchoscopy, peritoneoscopy, liver scan (US was not routinely used at the beginning), bilateral bone marrow trephine biopsy, and bone scan. Staging was discontinued when secondaries were detected in one, the more so as in two organs or systems (25 pts), and/or bronchoscopic contraindication for thoracotomy (11 pts), and this group of patients was out of the study. To 67 patients chemotherapy was given and after 3 courses these patients were reevaluated. In 21 patients PD, NC or CR was found. Forty six patients with PR underwent supplementary staging procedures: CT of the brain, CT of the upper retroperitoneal space and liver. Metastatic sites were found in 7 patients. Limited disease was identified in 39 patients. Limited-stage disease can be determined only after exclusion of extensive disease on the ground of: case history, physical assessment, X-ray of the chest (PA + lateral) + CT chest scan, bronchoscopy with biopsy or cytology, and outside the chest: 1. bone marrow trephbine biopsy and bone scan--bone marrow and skeleton, 2. CT head scan--brain, 3. CT abdominal scan--upper retroperitoneal space and liver.

[Initial concentration of the neoplastic biological markers AFP (alpha fetoprotein), HCG (chorionic gonadotropin), and SP1 (specific pregnancy protein) in separate types and stages of clinically advanced lung cancer]. / Wyjsciowe stezenia biologicznych markerów nowotworowych AFP (alfafetoproteiny), HCG (choriongonadotropiny kosmówkowej), SP1 (swoistego bialka ciazowego) w poszczególnych typach i stopniach zaawansowania klinicznego raka pluca.

Determination of neoplastic biological markers has been done in 709 patients including determination of AFP in 142, HCG in 324 and SP1 in 243 cases. Among 142 patients in whom AFP has been determined in 2 cases only (1.4%) the elevated level has been present. Elevated levels of HCG have been found in 19 out 324 cases (5.9%) and SP1 in 29 out 243 cases (11.9%).

Morphology and function of liver after intravenous and intraportal injections of the immunomodulating agent Propionibacterium granulosum.

An immunomodulator, cell walls from Propionibacterium granulosum strain KP-45 (PG), has been applied in rabbits to test its influence on morphology and function of liver cells. For investigation of distribution in internal organs, the PG preparation was 51Cr-labelled and injected i.v. into mice. Functional liver tests were performed in rabbits injected intravenously or intraportally with PG. Morphologic studies (light and electron microscopy) of liver sections were performed in mice and rats injected intravenously with PG, 1-60 d prior to liver examination. Intravenous or intraportal application of PG did not cause detectable clinical symptoms during the whole observation period (1-60 d). During the first 3-7 d, elevation of serum globulins and transaminases (SGOT, SGPT) were noted with reappearance of normal values after 14-20 d. 131I-labelled Bengal Rose injected into PG-treated rabbits was trapped mostly in the spleen, and to a smaller extent in liver, where radioactivity was significantly lower than in saline-injected control animals. 51Cr-labelled PG injected i.v. into mice were after 60-90 min localized preferentially in lungs and liver, where the radioactivity was much higher than in the spleen. Morphological studies revealed that 6 h following i.v. injection of PG, there appeared partial clearing of the hepatocyte cytoplasm and lowering of their basophilic content with enhancement of pinocytic activity of the hepatocytes. This was accompanied by enlargement of RES cells in liver with enhanced intracellular digestion, higher number of lysosomes and appearance of phagocytic vacuoles.(ABSTRACT TRUNCATED AT 250 WORDS)