Gestational diabetic patients with adequate management have normal cardiovascular autonomic regulation during the third trimester of pregnancy and 3 months after delivery

ObjectiveThe aim of the present study was to evaluate the influence of gestational diabetes mellitus (GDM) on hemodynamics and cardiovascular autonomic regulation at rest and their responses to head-up tilt (HUT).Research Design and MethodsWe prospectively studied 79 pregnant women (51 with GDM, 28 without GDM) during the third trimester of pregnancy and after parturition. The maternal electrocardiogram and arterial blood pressure were noninvasively measured. Heart rate and blood pressure were measured in the supine position and in the upright position. Stroke volume was assessed from noninvasive blood pressure signals, heart rate variability (HRV) was analyzed in frequency domain, and baroreflex sensitivity by the cross-spectral and sequence methods.ResultsBetween the GDM group and control pregnant women there were no significant differences in hemodynamics and cardiovascular autonomic regulation throughout the protocol. Increased normalized low-frequency component and low-frequency to high-frequency ratio suggested a change in sympathovagal balance towards sympathetic predominance during pregnancy in both groups. The response to head-up tilt (HUT) was similar in both GDM and control pregnant women. The pregnancy modulated the response to HUT in systolic and diastolic blood pressure, stroke volume, cardiac index, peripheral resistance, total power of HRV, and its low- and high-frequency components.ConclusionsOur results suggest that pregnancy modulates cardiovascular autonomic regulation and hemodynamics equally in subjects with GDM and without GDM, suggesting that metabolic disorder during pregnancy does not result in cardiovascular dysfunction when GDM is in good balance.     

An extensive tumor array analysis supports tumor suppressive role for nucleophosmin in breast cancer

Nucleophosmin (NPM) is a multifunctional protein involved in a complex network of interactions. The role of NPM in oncogenesis is controversial. The NPM gene (NPM1) is mutated or rearranged in a number of hematological disorders, but such changes have not been detected in solid cancers. However, experiments with cultured NPM-null cells and with mice carrying a single inactivated NPM allele indicate a tumor suppressor function for NPM. To resolve the role of NPM in solid cancers, we examined its expression and localization in histologically normal breast tissue and a large array of human breast carcinoma samples (n = 1160), and also evaluated its association with clinicopathological variables and patient survival. The intensity and localization (nucleolar, nuclear, cytoplasmic) of NPM varied across clinical samples. No mutations explaining the differences were found, but the present findings indicate that expression levels of NPM affected its localization. Our study also revealed a novel granular staining pattern for NPM, which was an independent prognostic factor of poor prognosis. In addition, reduced levels of NPM protein were associated with poor prognosis. Furthermore, luminal epithelial cells of histologically normal breast displayed high levels of NPM and overexpression of NPM in the invasive MDA-MB-231 cells abrogated their growth in soft agar. These results support a tumor suppressive role for NPM in breast cancer.     

Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or beta-cell hyperplasia in adult patients

CONTEXT AND OBJECTIVE: Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) is a promising method in localizing neuroendocrine tumors. Recently, it has been shown to differentiate focal forms of congenital hyperinsulinism of infancy. The current study was set up to determine the potential of 18F-DOPA PET in identifying the insulin-secreting tumors or beta-cell hyperplasia of the pancreas in adults. PATIENTS AND METHODS: We prospectively studied 10 patients with confirmed hyperinsulinemic hypoglycemia and presumed insulin-secreting tumor using 18F-DOPA PET. Anatomical imaging was performed with computed tomography (CT) and magnetic resonance imaging (MRI). All patients were operated on, and histological verification was available in each case. Semiquantitative PET findings in the pancreas using standardized uptake values were compared to standardized uptake values of seven consecutive patients with nonpancreatic neuroendocrine tumors. RESULTS: By visual inspection of 18F-DOPA PET images, it was possible in nine of 10 patients to localize the pancreatic lesion, subsequently confirmed by histological analysis. 18F-DOPA uptake was enhanced in six of seven solid insulinomas and in the malignant insulinoma and its hepatic metastasis. Two patients with beta-cell hyperplasia showed increased focal uptake of 18F-DOPA in the affected areas. As compared to CT or MRI, 18F-DOPA PET was more sensitive in localizing diseased pancreatic tissue. CONCLUSION: 18F-DOPA PET was useful in most patients with insulinoma and negative CT, MRI, and ultrasound results. In agreement with previous findings in infants, preoperative 18F-DOPA imaging seems to be a method of choice for the detection of beta-cell hyperplasia in adults. It should be considered for the detection of insulinoma or beta-cell hyperplasia in patients with confirmed hyperinsulinemic hypoglycemias when other diagnostic work-up is negative.     

Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes

Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.     

Patient satisfaction as a positive nursing outcome

The purpose of this cross-sectional survey was to assess patient satisfaction and analyze its relationship to nurse staffing levels in 34 inpatient wards at 4 Finnish university hospitals. The patients were satisfied with their care in general. However, the proportion of registered nurses (RNs), the patient-to-RN ratio, and the RNs' working years were highly related to patient satisfaction. Eight patients per RN was the cut-off point for patient satisfaction.     

Novel small molecule inhibitors for prostate-specific antigen

BACKGROUND: Prostate-specific antigen (PSA or KLK3) has been shown to inhibit angiogenesis, but it might also have tumor promoting activities. Thus, it may be possible to modulate prostate cancer growth by stimulating or inhibiting the activity of PSA. To this end we have previously identified peptides that stimulate the activity of PSA. As peptides have several limitations as drug molecules, we screened a chemical library to find drug-like compounds that could be used to modulate the function(s) of PSA. METHODS: Almost 50,000 compounds were analyzed for their ability to modulate PSA activity towards a fluorescent PSA-substrate. The ability of the most active compounds to affect the anti-angiogenic activity of PSA was analyzed by human umbilical vein endothelial cell (HUVEC) tube formation assay. RESULTS: In the initial screening we identified two compounds that inhibited PSA activity. Based on these, similar compounds were selected and tested for activity to define structure-activity relationships. Several compounds with micromolar IC50-values were found, but they were not entirely specific towards PSA, e.g., they inhibited chymotrypsin, which has similar substrate specificity as PSA. However, it was possibly to improve the selectivity of the compounds towards PSA by small structural changes. These compounds inhibited the anti-angiogenic activity of PSA in the HUVEC model, proving that the proteolytic activity of PSA is essential for inhibition of angiogenesis. CONCLUSIONS: We found several PSA inhibitors that could be useful tools for studying the role of PSA in cancer models and in normal physiology as showed in angiogenesis model.     

Effectiveness of hip or knee replacement surgery in terms of quality-adjusted life years and costs

BACKGROUND: Concurrent head-to-head comparisons of healthcare interventions regarding cost-utility are rare. The concept of favorable cost-effectiveness of total hip or knee arthroplasty is thus inadequately verified. PATIENTS AND METHODS: In a trial involving several thousand patients from 10 medical specialties, 223 patients who were enrolled for hip or knee replacement surgery were asked to fill in the 15D health-related quality of life (HRQoL) survey before and after operation. RESULTS: Mean (SD) HRQoL score (on a 0-1 scale) increased in primary hip replacement patients (n = 96) from 0.81 (0.084) preoperatively to 0.86 (0.12) at 12 months (p < 0.001). In revision hip replacement (n = 24) the corresponding scores were 0.81 (0.086) and 0.82 (0.097) respectively (p = 0.4), and in knee replacement (n = 103) the scores were 0.81 (0.093) and 0.84 (0.11) respectively (p < 0.001). Of 15 health dimensions, there were statistically significant improvements in moving, usual activities, discomfort and symptoms, distress, and vitality in both primary replacement groups. Mean cost per quality-adjusted life year (QALY) gained during a 1-year period was euro 6,710 for primary hip replacement, euro 52,274 for revision hip replacement, and euro 13,995 for primary knee replacement. INTERPRETATION: Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is twice that gained from hip replacement.     

Serum high-density lipoprotein cholesterol and risk of non-hodgkin lymphoma

Lymphoma patients often exhibit abnormal lipid metabolism. Recent evidence, however, suggests that a decrease in circulating high-density lipoprotein cholesterol (HDL-C) may occur during lymphomagenesis, reflecting underlying etiology such as inflammation. We investigated the relationship between prediagnostic HDL-C and non-Hodgkin lymphoma (NHL) in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. At baseline, serum HDL-C and total cholesterol concentrations from fasting blood, information on diet and lifestyle, and direct measurements of height, weight, and blood pressure were obtained from 27,074 healthy male smokers of ages 50 to 69 years. Cox proportional hazards models with age as underlying time metric was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). We found no association between total or non-HDL cholesterol and the 201 incident NHL cases ascertained during the follow-up (1985-2002), but observed an inverse association between HDL-C and NHL, which changed with length of follow-up. High HDL-C was associated with lower risk of all NHL during the first 10 years (n = 148; RR for 5th versus 1st quintile, 0.35; 95% CI, 0.19-0.62; P(trend) < 0.0001), but not with diagnoses during later follow-up (n = 53; RR, 1.31; 95% CI, 0.55-3.10). The inverse association was similar for NHL subtypes and was not modified by obesity, blood pressure, physical activity, or alcohol intake, but seemed to be stronger in men with lower duration of smoking (P(interaction) = 0.06). Our findings implicate HDL-C as a preclinical indicator of NHL and warrant further prospective investigations for its etiologic contribution.