Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared late complication. Treatment options are lacking at present. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with adipose-derived regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up. MATERIAL AND METHODS: We included 10 patients with BCRL. ADRCs were injected directly into the axillary region together with a scar-releasing fat grafting procedure. Primary endpoint was change in arm volume. Secondary endpoints were change in patient-reported outcomes, changes in lymph flow, and safety. RESULTS: During follow-up, no significant change in volume was noted. Patient-reported outcomes improved significantly with time. Five patients reduced their use of conservative management. Quantitative lymphoscintigraphy did not improve on the lymphedema-affected arms. ADRCs were well tolerated, and only minor transient adverse events related to liposuction were noted. CONCLUSIONS: In this pilot study, a single injection of ADRCs improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events during the follow-up period. Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There was no change in excess arm volume. Results of this trial need to be confirmed in randomized clinical trials.

Cardiac Abnormalities in Adult Patients With Polymyositis or Dermatomyositis as Assessed by Noninvasive Modalities.

OBJECTIVE: Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction. METHODS: In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac (99m) Tc-pyrophosphate ((99m) Tc-PYP) scintigraphy. RESULTS: Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P = 0.02) and longer QRS and QT intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis-specific or -associated autoantibodies (P = 0.05), and high cardiac (99m) Tc-PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. CONCLUSION: Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis-specific or -associated autoantibodies and high cardiac (99m) Tc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM.

Systemic nitric oxide clamping in normal humans guided by total peripheral resistance.

AIM: We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. METHODS: Normal volunteers (23-28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) at 0.5 mg kg(-1) h(-1). One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l-NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. RESULTS: l-NAME increased MABP and total peripheral resistance (TPR, 1.02 + or - 0.05 to 1.36 + or - 0.07 mmHg s mL(-1), mean + or - SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 + or - 0.05 mmHg s mL(-1), P < 0.05). CO decreased with l-NAME (5.8 + or - 0.3 to 4.7 + or - 0.3 L min(-1), P < 0.01) and returned to control when SNP was added (6.0 + or - 0.3 L min(-1)). A decrease in plasma noradrenaline (42%, P < 0.01) during l-NAME administration was completely reversed by SNP. Plasma renin activity decreased during l-NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l-NAME and remained elevated. CONCLUSIONS: Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.

Effects of oxytocin in normal man during low and high sodium diets.

AIM: We tested the hypothesis that oxytocin in normal man causes natriuresis by means of nitric oxide and/or atrial natriuretic peptide. METHODS: Normal male subjects were investigated after 4 days of sodium controlled diets (30 mmol sodium chloride day(-1), n = 8 or 230 mmol sodium chloride day(-1), n = 6). Oxytocin was infused intravenously (1 pmol kg(-1) min(-1) for 240 min). RESULTS: Mean arterial blood pressure, heart rate and glomerular filtration rate by clearance of chromium-labelled ethylenediaminetetraacetate remained stable. Plasma oxytocin increased from 2 to 3 pg mL(-1) to around 50 pg mL(-1). Oxytocin decreased urine flow (4.2 +/- 0.2--0.75 +/- 0.11 and 4.6 +/- 1.3-1.4 +/- 0.6 mL min(-1), low- and high-salt diet, respectively). During low-salt conditions, oxytocin reduced sodium and potassium excretion (11 +/- 2--4 +/- 2 and 93 +/- 19--42 +/- 3 micromol min(-1), respectively). Plasma renin, angiotensin II, aldosterone and renal excretion of metabolites of nitric oxide (nitrate and nitrite) all decreased. Plasma atrial natriuretic peptide and cyclic guanosine monophosphate were unchanged. A similar pattern was obtained during high-salt conditions but in this case the antinatriuresis was not different from that occurring during the corresponding time control series. CONCLUSIONS: The data reject the hypothesis. In contrast, we found significant antinatriuretic, antikaliuretic and antidiuretic effects, which were not mediated by the renin-angiotensin-aldosterone system, atrial natriuretic peptide, systemic haemodynamics, or processes increasing urinary excretion of metabolites of nitric oxide. The natriuretic effect of oxytocin found in laboratory animals is species-specific.

Mechanisms of acute natriuresis in normal humans on low sodium diet.

This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin-angiotensin-aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day(-1)) received isotonic saline intravenously (NaLoading: 20 micromol Na(+) kg(-1) min(-1) or approximately 11 ml min(-1) for 240 min). NaLoading did not change MAP or GFR (by clearance of (51)Cr-EDTA). Significant natriuresis occurred within 1 h (from 9 +/- 3 to 13 +/- 2 micromol min(-1)). A 6-fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related (R = 0.997) as were ANGII and aldosterone (R = 0.999). The slopes were 0.40 pM ANGII (mi.u. renin activity)(-1) and 22 pM aldosterone (pM ANGII)(-1). Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NO(x)). In conclusion, sodium excretion may increase 7-fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP- and NO(x) excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII-mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.

[Aortic stenosis as a cause of protein-losing enteropathy]. / Aortastenose som årsag til proteintabende enteropati.

A case of protein-losing enteropathy associated with aortic stenosis and without signs of right-sided heart failure is described. The protein loss was diagnosed and quantitated by 111Indium-transferrin imaging and whole-body retention. The intestinal loss of protein decreased from 35% to 5% after implantation of a mechanical aorta valve.