Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists

Despite the fact that consensus guidelines recommend long-term dopamine agonist (DA) therapy as a first-line approach to the treatment of small prolactinoma, some patients continue to prefer a primary surgical approach. Concerns over potential adverse effects of long-term medical therapy and/or the desire to become pregnant and avoid long-term medication are often mentioned as reasons to pursue surgical removal. In this retrospective study, 34 consecutive patients (30 female, 4 male) preferably underwent primary pituitary surgery without prior DA treatment for small prolactinomas (microprolactinoma 1–10 mm, macroprolactinoma 11–20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients with microprolactinomas had significantly lower preoperative prolactin (PRL) levels compared to patients with macroprolactinomas (median 143 μg/l vs. 340 μg/l). Ninety percent of symptomatic patients experienced significant improvement of their signs and symptoms upon surgery. The postoperative PRL levels (median 3.45 μg/l) returned to normal in 94% of patients with small prolactinomas. There was no mortality and no major morbidities. One patient suffered from hypogonadotropic hypogonadism after surgery despite postoperative normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%) with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas after a median follow-up period of 33.5 months. Patients with small prolactinomas can safely consider pituitary surgery in a specialized centre with good chance of long-term remission as an alternative to long-term DA therapy

Carbon Monoxide Promotes Respiratory Hemoproteins Iron Reduction Using Peroxides as Electron Donors

The physiological role of the respiratory hemoproteins (RH), hemoglobin and myoglobin, is to deliver O2 via its binding to their ferrous (FeII) heme-iron. Under variety of pathological conditions RH proteins leak to blood plasma and oxidized to ferric (FeIII, met) forms becoming the source of oxidative vascular damage. However, recent studies have indicated that both metRH and peroxides induce Heme Oxygenase (HO) enzyme producing carbon monoxide (CO). The gas has an extremely high affinity for the ferrous heme-iron and is known to reduce ferric hemoproteins in the presence of suitable electron donors. We hypothesized that under in vivo plasma conditions, peroxides at low concentration can assist the reduction of metRH in presence of CO. The effect of CO on interaction of metRH with hydrophilic or hydrophobic peroxides was analyzed by following Soret and visible light absorption changes in reaction mixtures. It was found that under anaerobic conditions and low concentrations of RH and peroxides mimicking plasma conditions, peroxides served as electron donors and RH were reduced to their ferrous carboxy forms. The reaction rates were dependent on CO as well as peroxide concentrations. These results demonstrate that oxidative activity of acellular ferric RH and peroxides may be amended by CO turning on the reducing potential of peroxides and facilitating the formation of redox-inactive carboxyRH. Our data suggest the possible role of HO/CO in protection of vascular system from oxidative damage

Dopaminergic and Serotonergic Drug Use: A Nationwide Register-Based Study of Over 1 300 000 Older People

Objective: To investigate the use of dopaminergic and serotonergic drugs in elderly people. Methods: We analyzed data on age, sex and dispensed drugs for individuals aged $65 years registered in the Swedish Prescribed Drug Register from July to September 2008 (n = 1 347 564; 81$65 years in Sweden). Main outcome measures were dopaminergic (enhancing and/or lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of these. Results: Dopaminergic and serotonergic drugs were used by 5.6 % and 13.2 % the participants, respectively. Female gender was related to use of both dopaminergic and, particularly, serotonergic drugs. Higher age was associated with use of dopamine lowering drugs and serotonergic drugs, whereas the association with use of dopamine enhancing drugs declined in the oldest old. The occurrence of combinations of dopaminergic and serotonergic drugs was generally low, with dopamine lowering + serotonin lowering drug the most common combination (1.6%). Female gender was associated with all of the combinations of dopaminergic and serotonergic drugs, whereas age showed a mixed pattern. Conclusion: Approximately one out of ten older patients uses serotonergic drugs and one out of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic drugs in the elderly patients is a potential problem due to the fact that aging is associated with a down-regulation of both these monoaminergic systems. Future studies are needed fo

Environmental Enrichment Promotes Plasticity and Visual Acuity Recovery in Adult Monocular Amblyopic Rats

Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. In some occasions, amblyopic patients loose vision in their better eye owing to accidents or illnesses. While this condition is relevant both for its clinical importance and because it represents a case in which binocular interactions in the visual cortex are suppressed, it has scarcely been studied in animal models. We investigated whether exposure to environmental enrichment (EE) is effective in triggering recovery of vision in adult amblyopic rats rendered monocular by optic nerve dissection in their normal eye. By employing both electrophysiological and behavioral assessments, we found a full recovery of visual acuity in enriched rats compared to controls reared in standard conditions. Moreover, we report that EE modulates the expression of GAD67 and BDNF. The non invasive nature of EE renders this paradigm promising for amblyopia therapy in adult monocular people

Prospective evaluation of weekly concomitant tumor bed boost with three-week hypofractionated whole breast irradiation in early breast cancer

Objectives: A prospective study was conducted to assess the acute and late toxicity of hypofractionated whole breast irradiation with a weekly concomitant boost for women with early breast cancer (EBC). Methods: Women with EBC who underwent breast-conserving surgery were eligible. A dose of 40Gy in 15 fractions over 3 weeks was delivered to the whole breast with a concomitant weekly boost to the post-operative cavity of 3Gy in three fractions. Toxicity was graded using the Radiation Therapy Oncology Group (RTOG) acute toxicity and RTOG/EORTC late toxicity scales. Results: A total of 67 women were enrolled with a median age of 49 years (range 31–69). Median follow-up was 25 months (range 11–34). Acute skin reactions included grade (G) 1 (n = 47, 70%), G2 (n = 10, 13%), and G3 (n = 1, 1.5%). Late skin toxicity was observed in 13 patients (19%), all of whom experienced G1 toxicity only. On multivariable analysis, diabetes mellitus was predictive of acute skin toxicity (p = 0.003), while age less than 50 years (p = 0.029) and diabetes mellitus (p = 0.013) were predictive of late skin toxicity. Conclusions: Whole breast irradiation with concomitant weekly boost appears feasible and safe. Further investigation is required to fully evaluate this schedule as an alternative to conventional whole breast irradiation with a sequential boost

Dopaminergic and Serotonergic Drug Use: A Nationwide Register-Based Study of Over 1 300 000 Older People

OBJECTIVE: To investigate the use of dopaminergic and serotonergic drugs in elderly people. METHODS: We analyzed data on age, sex and dispensed drugs for individuals aged ≥65 years registered in the Swedish Prescribed Drug Register from July to September 2008 (n = 1,347,564; 81% of the total population aged ≥65 years in Sweden). Main outcome measures were dopaminergic (enhancing and/or lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of these. RESULTS: Dopaminergic and serotonergic drugs were used by 5.6% and 13.2% the participants, respectively. Female gender was related to use of both dopaminergic and, particularly, serotonergic drugs. Higher age was associated with use of dopamine lowering drugs and serotonergic drugs, whereas the association with use of dopamine enhancing drugs declined in the oldest old. The occurrence of combinations of dopaminergic and serotonergic drugs was generally low, with dopamine lowering + serotonin lowering drug the most common combination (1.6%). Female gender was associated with all of the combinations of dopaminergic and serotonergic drugs, whereas age showed a mixed pattern. CONCLUSION: Approximately one out of ten older patients uses serotonergic drugs and one out of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic drugs in the elderly patients is a potential problem due to the fact that aging is associated with a down-regulation of both these monoaminergic systems. Future studies are needed for evaluation of the impact of these drugs on different cognitive and emotional functions in old age

Co-morbidity and polypharmacy in Parkinson's Disease:insights from a large Scottish primary care database

Background: Parkinson’s disease is complicated by comorbidity and polypharmacy, but the extent and patterns of these are unclear. We describe comorbidity and polypharmacy in patients with and without Parkinson’s disease across 31 other physical, and seven mental health conditions. Methods: We analysed primary health-care data on 510,502 adults aged 55 and over. We generated standardised prevalence rates by age-groups, gender, and neighbourhood deprivation, then calculated age, sex and deprivation adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for those with PD compared to those without, for the prevalence, and number of conditions. Results: Two thousand six hundred forty (0.5%) had Parkinson’s disease, of whom only 7.4% had no other conditions compared with 22.9% of controls (adjusted OR [aOR] 0.43, 95% 0.38–0.49). The Parkinson’s group had more conditions, with the biggest difference found for seven or more conditions (PD 12.1% vs. controls 3.9%; aOR 2.08 95% CI 1.84–2.35). 12 of the 31 physical conditions and five of the seven mental health conditions were significantly more prevalent in the PD group. 44.5% with Parkinson’s disease were on five to nine repeat prescriptions compared to 24.5% of controls (aOR 1.40; 95% CI 1.28 to 1.53) and 19.2% on ten or more compared to 6.2% of controls (aOR 1.90; 95% CI 1.68 to 2.15). Conclusions: Parkinson’s disease is associated with substantial physical and mental co-morbidity. Polypharmacy is also a significant issue due to the complex nature of the disease and associated treatments

The Relevance of Breast Cancer Subtypes in the Outcome of Neoadjuvant Chemotherapy

BACKGROUND: Breast cancer is increasingly considered a heterogeneous disease. The aim of this study was to assess the differences between histological and receptor-based subtypes in breast-conserving surgery and pathological complete response (pCR) after neoadjuvant chemotherapy. METHOD: A consecutive series of 254 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Tumors were classified according to their receptor status in estrogen receptor (ER)-positive tumors (HER2-negative), triple-negative tumors, and HER2-positive tumors. The type of surgery feasible prior to neoadjuvant chemotherapy was compared with the actual surgery performed. RESULTS: The overall increase in breast-conserving surgery was 37% (73 of 198). In patients with ductal and lobular carcinomas this increase was 41% (63 of 152, 95% confidence interval [95% CI] 0.34-0.49) and 20% (7 of 35, 95% CI 0.10-0.36), respectively (P = 0.02). Half of the patients with lobular carcinoma had to undergo a secondary mastectomy because of incomplete resection margins. In ER-positive, triple-negative and HER2-positive tumors, the increase in breast-conserving surgery was 39% (42 of 109, 95% CI 0.30-0.48), 24% (11 of 45, 95% CI 0.14-0.38), and 45% (20 of 44, 95% CI 0.32-0.60) (P = 0.11). The pCR rate in ductal and lobular carcinomas was 12% (23 of 195) and 2% (1 of 42), respectively (P = 0.09). In ER-positive, triple-negative and HER2-positive tumors the pCR rates were 2% (3 of 138), 28% (16 of 57), and 18% (10 of 56), respectively. Multivariate analysis showed that the receptor-based subtype was the only significant predictor of pCR (P = 0.004). CONCLUSION: In lobular tumors the benefit with regard to breast-conserving surgery of neoadjuvant chemotherapy is questionable. Although in ER-positive tumors the pCR rate is low, the increase in breast-conserving surgery was remarkable in ductal ER-positive tumor