Upper Extremity Lymphedema After Axillary Lymph Node Dissection: Prospective Lymphoscintigraphic Evaluation.

This prospective study was designed to evaluate changes in upper extremity lymphatic drainage after ALND in comparison to the preoperative status using lymphoscintigraphy. The study enrolled 44 women (mean age: 57.95; range: 35-80) with a new diagnosis of unilateral invasive breast carcinoma who had been scheduled to undergo ALND. This was a substudy of the physiotherapeutic project, in which subjects after ALND were randomized into 4 groups treated with: 1) rehabilitation exercises; 2) manual lymphatic drainage; 3) pneumatic compression pump; and 4) education only. Clinical evaluation which included arm measurements and lymphoscintigraphy was performed in every subject before surgery and 3 times after surgery (1-6 weeks, 1 and 2 years after ALND). Follow-up was completed in 44 subjects at 1 year and in 32 subjects at 2 years. Lymphedema diagnosis was made in 4 subjects 1 year after ALND (9%) and in 8 subjects 2 years after ALND (25%). Among them, respectively, only 50% and 62% noticed and reported lymphedema. Quantitative analysis of lymphoscintigrams and photoplethysmography results did not reveal upper extremities lymphatic transport and/or venous function impairment after the ALND procedure. Qualitative analysis of lymphoscintigrams revealed most commonly disappearance of previously functional lymph nodes and appearance of dermal backflow in subjects who developed lymphedema. Conversely, appearance of functional lymph nodes in different locations after ALND may indicate protection from development of upper extremity lymphedema.

Cardiovascular disease risk factors associated with low level of physical activity in postmenopausal Polish women.

OBJECTIVES: To determine whether physical activity level could have an effect on cardiovascular disease (CVD) risk factors in Polish postmenopausal women. METHODS: We studied the associations of physical activity (PA) level with obesity indices, unfavorable lipid profile parameters and the insulin resistance index HOMA in 343 postmenopausal Polish women selected from an urban population, aged 50-60. RESULTS: In the tested sample, a low level of PA significantly increased odds ratios for CVD risk factors such as BMI ≥ 30 kg/m(2), total body fat (TBF) > 75 th percentile, gynoid fat deposit (GFD) > 75 th percentile, total cholesterol (TC) ≥ 5 mM, low-density lipoprotein cholesterol (LDL-C) > 3 mM and HOMA ≥ 1.95. CONCLUSIONS: Obesity and some metabolic CVD risk factors in postmenopausal women are directly associated with low PA level. Postmenopausal urban women should be persuaded to be physically active, as even moderate activity level seems to be sufficient to reduce the CVD risk in this group of individuals.

ADRB3 and PPARγ2 gene polymorphisms and their association with cardiovascular disease risk in postmenopausal women.

OBJECTIVES: The contribution of heritability to the development of cardiovascular disease (CVD) is of interest as the identification of genes enhancing the susceptibility of individuals to CVD may help the design of clinical interventions optimized for the individual's genome. METHODS: We studied the associations of polymorphism of ADRB3 and PPARγ2 genes with obesity indices, unfavorable lipid profile parameters and insulin resistance index HOMA in 343 postmenopausal women. RESULTS: No association was found between tested polymorphisms and CVD risk factors such as total cholesterol ≥ 5.0 mmol/l, high density lipoprotein cholesterol < 1.2 mmol/l, low density lipoprotein cholesterol > 3.0 mmol/l and triacylglycerols > 1.7 mmol/l. The presence of arterial hypertension and HOMA value ≥ 1.95 were also not related to these polymorphisms. A significant association between PPARγ2 gene polymorphism and total body fat mass (odds ratio = 1.90 at p = 0.037) as well as android fat deposit mass (odds ratio = 1.82 at p = 0.048) was found. CONCLUSIONS: CVD risk factors in postmenopausal women are not directly associated with the polymorphisms of PPARγ2 and ADRB3 genes. We suggest that some indirect link between PPARγ2 gene polymorphism and susceptibility of postmenopausal women to CVD may exist. This suggestion is based on our finding that high total body fat mass and high android fat deposits are associated with the presence of the Pro12Ala allele of the PPARγ2 gene.

Axillary lymph nodes and arm lymphatic drainage pathways are spared during routine complete axillary clearance in majority of women undergoing breast cancer surgery.

Alterations in axillary lymph nodes (ALNs) after complete axillary lymph node dissection (ALND) in comparison to the preoperative status were evaluated using lymphoscintigraphy performed preoperatively and 1-6 weeks after surgery in 30 women with a new diagnosis of unilateral, invasive breast carcinoma. Analysis of lymphoscintigrams revealed that ALNs after surgery were present in 26 of 30 examined women. In comparison to preoperative status, they were visualized in the same location (12 women), in the same and additionally in different locations (9 women), or only in different locations (4 women). No lymph nodes were visualized in one woman and lymphocoele were in 4 women. Thus, after ALND, a variable number of axillary lymph nodes remain and were visualized on lymphoscintigraphy in the majority of women. The classical ALND, therefore, does not allow complete dissection and removal of axillary nodes with total disruption of axillary lymphatic pathways, accounting in part for the variable incidence and severity of lymphedema after the procedure.

Are endocannabinoid type 1 receptor gene (CNR1) polymorphisms associated with obesity and metabolic syndrome in postmenopausal Polish women?

OBJECTIVE: The aim of this study was to determine whether genetic variation at the cannabinoid receptor-1 (CNR1) locus could have an effect on adiposity, fat distribution and obesity-related metabolic disorders in Polish postmenopausal women. DESIGN AND SUBJECTS: The A3813G (rs12720071), G1422A (rs1049353), A4895G (rs806368) and rs806381, rs10485170, rs6454674 and rs2023239 single-nucleotide polymorphisms of CNR1 were genotyped in 348 randomly selected postmenopausal women aged 50-60 years recruited from the Wroclaw city population. MEASUREMENTS: CNR1 genotypes, anthropometric measures (body mass index (BMI), waist circumference (WC) and body fat distribution by dual energy X-ray absorptiometry) and metabolic parameters (glucose, lipid profile and Fasting Insulin Resistance Index for insulin resistance) were determined. RESULTS: The 3813G allele was not significantly associated with higher body mass, BMI, WC, total fat or fat percentage, but was associated with higher android fat deposit (2971.78±1655.08 vs 2472.64±1300.53, P=0.007) and percentage of android fat (37.59±8.45 vs 35.66±7.63, P=0.062). No associations for the G1422A, A4895G, rs806381, rs10485170, rs6454674 and rs2023239 variants were observed. CONCLUSIONS: There is an association of the variants of CNR1 with obesity-related phenotypes in Polish postmenopausal women. As cannabinoid receptor type 1 is a drug target for obesity, pharmacogenetic receptor gene analysis of obesity treatment by endocannabinoid blockade may be of interest to identify the best responders.

Melkersson-Rosenthal syndrome: lymphoscintigraphy-documented impairment and restoration of facial lymphatic drainage in the course of disease.

Melkersson-Rosenthal syndrome (MRS) is an idiopathic, rare disorder manifested by facial swelling, congenital plicated tongue and recurrent peripheral facial nerve palsy. Labial involvement alone is referred to as cheilitis granulomatosa. Differential diagnosis of MRS includes allergic angioedema, bacterial, viral or filarial infections as well as autoimmunological inflammation in the course of systemic lupus erythematosus, dermatomyositis, and others. We present 4 patients who experienced periodically painless edema of the face and/or lips. Lesions were diagnosed as recurrent Quincke's edema and were treated with antihistamine agents and glucocorticoids without improvement. In all four cases of MRS, we were able to document impaired lymphatic drainage from the swollen area using lymphoscintigraphy. We also documented in follow-up lymphoscintigraphy a restoration of lymphatic flow in three of the four patients with MRS and these results corresponded with clinical improvement. We have demonstrated that lymphatic pathology plays an important role in pathophysiology of chronic facial swelling in patients with Melkersson-Rosenthal syndrome.

Relationship of PPARgamma2 polymorphism with obesity and metabolic syndrome in postmenopausal Polish women.

OBJECTIVE: The contribution of genetic factors to the development of menopausal obesity has been widely recognized. Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in adipocyte differentiation and has been suggested to influence insulin sensitivity. The aim of this study was to evaluate the frequency of Pro12Ala PPARgamma polymorphism and its association with body mass index (BMI) and metabolic syndrome parameters in postmenopausal Polish women. MATERIAL AND METHODS: The study was performed in 318 postmenopausal women aged 50-60 years randomly selected from the Wroclaw city population with BMI ranging from 17.5 to 46.38 kg/m (2) (mean BMI 27.5+/-4.78 kg/m(2)). Anthropometric parameters, body composition (total body fat, android and gynoid deposits, using DXA) and biochemical parameters (lipid profile, glucose, and insulin levels) were measured and QUICKI was calculated. PPARgamma genotyping was performed by PCR and minisequencing using an ABI 310 sequencer (Applied Biosystems). RESULTS: The Pro12Ala genotype was found in 26% of the women, but Ala12Ala only in 4%. Metabolic syndrome was recognized in 16% of all the women, 14% of the women with Pro12Pro genotype, 21% of the Pro12Ala carriers, and 14% of the women with the Ala12Ala variant. Obese women with at least one Ala allele (X/Ala genotype) showed higher serum levels of total cholesterol (265.7+/-44.5 mg/dl vs. 233.2+/-38.1 mg/dl, p<0.001), LDL cholesterol (171.8+/-37.8 mg/dl vs. 143.7+/-34.8 mg/dl; p<0.001), and triglycerides (149.4+/-55.2 mg/dl vs. 126.8+/-54.2 mg/dl, p<0.05) compared with the women with the Pro12Pro genotype. CONCLUSIONS: The Pro12Ala PPARgamma polymorphism does not seem to be associated with BMI or metabolic syndrome parameters in postmenopausal Polish women, although the X/Ala genotype seems to predispose to a less favorable lipid profile in this population.

Metastases to the internal mammary lymph nodes as the only spread of ductal breast cancer: case description.

The present paper describes a case of a breast cancer patient in whom lymphoscintigraphy identified metastases in the internal mammary nodes whilst the axillary lymphatic center was tumor-negative. Because of the lymph node involvement, cancer was restaged from original I to IIIc. Consequently, the patient was qualified for chemotherapy with docetaxel and doxorubicin. The case described is another contribution for the routine application of sentinel lymph node biopsy (SLNB) in breast cancer patients.

Presence of functional axillary lymph nodes and lymph drainage within arms in women with and without breast cancer-related lymphedema.

This pilot study was designed to investigate lymphatic transport in the arms of women after breast cancer treatment without lymphedema and with mild and severe arm lymphedema. Nineteen breast cancer survivors [6 without (Group 1), 6 with mild (Group 2) and 7 with severe (Group 3) lymphedema] were examined. Lymphatic transport in the arm and to axillary lymph nodes were evaluated using quantitative radionuclide lymphscintigraphy. The radioactivity ratio between the operated and unoperated axillae (axillary ratio), and both lymphatic transport and tracer disappearance rates (TDR) from the injection sites were calculated. We found that axillary ratio and lymphatic transport were significantly higher in Groups 1 and 2 compared to 3 and that TDR was not affected in any Group. Additionally, lymphscintigraphy revealed presence of functional axillary lymph nodes within the operated axilla in women without or with mild lymphedema, while in women with severe lymphedema, no axillary lymph nodes were visualized. We conclude from our subjects that breast cancer survivors who did not develop or had mild arm lymphedema have functional lymphatic transport and lymph nodes in the axillary area on the operated side. This suggests that efficient collateral circulation and/or peripheral lymphovenous communications has developed in these subjects which may be preventative for the development of severe lymphedema.

Prevalence of obesity in Poland.

Obesity is an important health problem in Poland affecting adolescents and adults. A study of a Lower Silesian population aged 20-40 years (25 400 participants), between 1993 and 2003, showed an increase in obese women from 8.9% to 15.0%, but no change in men (6.3% vs. 6.5%, respectively). Obesity occurs more frequently in girls and women (6% and 15%) compared to boys and men (4.0% and 6.5%, respectively). Estimation of obesity prevalence in various parts of Poland seems to be regionally dependent; the highest prevalence of obesity was observed in eastern regions of Poland.

Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis.

BACKGROUND: Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men. MATERIAL AND METHODS: We investigated 86 men aged 40-60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx (+) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods. RESULTS: Men with coronary artery disease had lower total testosterone levels (17.01+/-6.42 vs. 19.37+/-6.58 nmol/l; p < 0.05), testosterone/estradiol ratio (228.5+/-88.5 vs. 289.8+/-120.1; p < 0.05) and free androgen index (FAI) (59.49+/-14.79 vs. 83.03+/-25.81; p < 0.0001), and higher levels of estrone (49.5+/-27.7 vs. 36.6+/-12.7 pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (p < 0.05) between testosterone level and serum level of glucose (r = -0.29), triglycerides (r= -0.37), body mass index (r= -0.55), waist (r = - 0.43), total body fat mass (r = - 0.3) and fasting insulin resistance index. A significant positive association (p < 0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (r = 0.26). CONCLUSIONS: Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.

Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism.

Many animal and human studies show that supraphysiological doses of dehydroepiandrosterone (DHEA) can influence body composition and carbohydrate and lipid metabolism. Most studies have concentrated on women and have not been randomized, thus creating controversial results. With this in mind, we designed a cross-over double-blind placebo-controlled study of 12 men aged 59.0 +/- 4.8 years, who received either 50 mg/24 h DHEA or placebo for 3 months to assess the influence of DHEA on the content and distribution of fat tissue and serum insulin, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels, as well as testosterone, estradiol, DHEA-sulfate (S), prostate-specific antigen (PSA) concentrations and indexes of insulin sensitivity and resistance. Patients were recruited from university employees attending for periodic health checks, with normal hepatic and renal function with endogenous DHEA-S level < 1500 ng/dl. Our results did not reveal any significant changes in study parameters, apart from a statistically significant increase in DHEA-S levels after therapy with active substance.

Influence of dietary and genetic factors on metabolic status in obese and lean postmenopausal women.

This preliminary study addressed the possible associations between dietary, genetic and hormonal factors that are involved in the development of menopausal obesity and its metabolic consequences. We performed anthropometrical, hormonal and biochemical measurements and used a nutritional questionnaire on 43 postmenopausal women who were non-HRT-users (14 obese and 29 non-obese subjects, mean age +/- SD of 52.8 +/- 4.6 years, mean body mass 74.6 +/- 4.6 kg). All of the women also had fat mass assessed by DPX-Lunar. From the 24-h dietary recall, the nutrient intake in daily food rations was calculated using a computer program (Nutritionist IV, San Bruno, CA, USA) based on our own database. Restriction fragment length polymorphism of the estrogen-receptor-alpha gene was determined with the PvuII restriction enzyme. Obese women widely under-reported their daily food intake. The analysis of body fat distribution showed that the total body weight and the percentage of total fat mass were significantly increased in the obese group (p = 0.001). We observed significantly higher leptin (20.56 +/- 11.9 vs. 9.02 +/- 2.8 ng/ml) and total cholesterol (but lower cholesterol HDL), triglycerides levels in the obese subjects (261.89 +/- 48.8 vs. 248.23 +/- 55.9; 52.17 +/- 13.6 vs. 60.92 +/- 13.04; 142.82 +/- 61.02 vs. 106.61 +/- 27.7 mg/dl). Except for diastolic blood pressure, clinical variables were not significantly different between subjects with and without the PvuII ERalpha polymorphism. Allele frequencies of the ERalpha polymorphism did not differ from those previously reported (P-0.48, p-0.52) in our study. In this preliminary study we failed to find dietary and genetic factors involved in the pathogenesis of menopausal obesity. However, our results provide support for the notion that the perimenopausal increase in visceral fat is a significant factor involved in the increased cardiovascular risk in postmenopausal women.

Quantitative ultrasound of the heel and some parameters of bone turnover in patients with acromegaly.

Acromegaly caused by growth hormone (GH) hypersecretion is characterized by enhanced skeletal growth and soft tissue enlargement. Insulin-like growth factor-1 (IGF-1) is the main peripheral mediator of GH action and it has a crucial role in the maintenance of a normal bone mass. However, in some patients with acromegaly, secondary osteoporosis is observed, despite the strong anabolic effect of GH and IGF-1 in bones. It is thought to be due to hypogonadism. The bone changes are accompanied by increased turnover. The aim of this study was to assess bone properties by ultrasound and turnover in patients with acromegaly. The study was carried out in 26 patients (13 men, 13 women): 14 with active acromegaly and 12 cured by surgery who had non-active disease. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and their combination Stiffness Index (SI) by quantitative ultrasound (QUS) of the heel, hormonal status, serum osteocalcin (OC) concentration and the urinary excretion of pyridinoline collagen crosslinks (PYR) were all studied. Controls were 20 age- and sex-matched healthy persons. We observed statistically significantly lower QUS values in patients with active disease than in those whose disease was cured. The differences were more pronounced in men. QUS values were lower in the entire group of patients compared with the controls; however, the differences were not statistically significant. Serum OC concentrations and urinary PYR excretion were higher in active disease. Statistically significant inverse correlations between serum GH levels and SOS (r = -0.58, p = 0.002); BUA (r = -0.66; p = 0.0001); T-score (r = -0,65, p = 0.0001) and Z-score (r = -0.66, p = 0.0001) were found only in male patients. No correlations between IGF-1, duration of the disease, OC, PYR and other data studied were observed. In conclusion, we have shown decreased QUS parameters suggesting impaired bone properties and quality in terms of density and elasticity in men, but not in women, with active acromegaly. This finding suggests osteoporosis with increased bone turnover. The above-mentioned changes might be caused by the action of GH on trabecular bone and its metabolism, since no hypogonadism in male patients was shown. Moreover, the influence of acromegaly on heel geometry and soft tissue swelling should also be considered.

[Function of endogenous opioid peptides and sex steroids at the level of the central nervous system]. / Dzialanie endogennych peptydów opioidowych i steroidów plciowych na poziomie osrodkowego ukladu nerwowego.

Gonadal steroids and beta-endorphin (beta-EP) (and probably other - EOP endogenous opioid peptides) play a role of the pivotal hormones involved in integration of several neurophysiological mechanisms. The reproductive system could be disturbed at hypothalamic level by interference of beta-EP and GnRH secretion and/or at pituitary level with response of gonadotropes to GnRH. Gonadal steroids, through a feedback mechanism, may exert similar effect on hypothalamus and/or pituitary. The action of EOP on the hypothalamo-pituitary-gonadal axis may be influenced by physiological and pathological changes in gonadal steroids during puberty, menstrual cycle in females, menopause, in case of idiopathic delayed puberty, in patients with gonadal dysgenesis or after castration. EOP seems to be "gonadostat" system that have a key role in the transmission of gonadal feedback signals to the brain.

Bombesin plasma levels in patients with benign and malignant breast disease.

Some reports suggest a role for bombesin-like peptides in the pathology of breast tumors. Bombesin and related gastrin-releasing peptides have been shown to influence the inositol phospholipid signalling pathway and stimulate growth of some cells, including some human breast cancer cell lines. We measured the plasma concentration of bombesin in 23 breast cancer patients, 32 patients suffering from benign breast disease and in 21 healthy controls. The bombesin concentration in plasma taken from the thoracodorsal vein, in the vicinity of the tumor in breast cancer patients was higher than that in the peripheral circulation (mean +/- SEM, 91.3 +/- 54.3 vs. 40.9 +/- 27.4 pg/ml; p < 0.05). Bombesin concentrations in the cubital vein in breast cancer patients and in those with benign breast disease (61.7 +/- 49.3 pg/ml) was significantly higher than that in the control group (23.7 +/- 5.06 pg/ml; p < 0.05). Our findings suggest storage or synthesis of bombesin-like peptides within the affected breast and may confirm the role of these peptides in the growth of breast tumors.