Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN). It has been suggested that microglial inflammation augments the progression of PD. Neuromelanin (NM), a complex polymer pigment found in catecholaminergic neurons, has sparked interest because of the suggestion that NM is involved in cell death in Parkinson's disease, possibly via microglia activation. To further investigate the possible role of NM in the pathogenesis of PD, we conducted in vivo experiments to find out whether microglial cells become activated after injection of human neuromelanin (NM) into (1) the cerebral cortex or (2) the substantia nigra to monitor in this PD-relevant model both microglial activation and possible neurodegeneration. In this study, adult male Wistar rats received an intracerebral injection of either NM, bacterial lipopolysaccharide (LPS, positive control), phosphate-buffered saline (PBS, negative control) or colloidal gold suspension (negative particular control). After different survival times (1, 8 or 12 weeks), brain slices from the cerebral cortex or substantia nigra (SN, 1 week) were stained with Iba-1 and/or GFAP antibody to monitor microglial and astrocytic reaction, and with tyrosine hydroxylase (TH) to monitor dopaminergic cell survival (SN group only). The injection of LPS induced a strong inflammatory response in the cortex as well in the substantia nigra. Similar results could be obtained after NM injection, while the injection of PBS or gold suspension showed only moderate or no glial activation. However, the inflammatory response declined during the time course. In the SN group, there was, apart from strong microglia activation, a significant dopaminergic cell loss after 1 week of survival time. Our findings clearly indicate that extracellular NM could be one of the key molecules leading to microglial activation and neuronal cell death in the substantia nigra. This may be highly relevant to the elucidation of therapeutic strategies in PD.     

Isolated atrioventricular discordance. Report of two surgical cases with isolated ventricular inversion

Isolated ventricular inversion is a term used for a congenital heart malformation with the segmental arrangement atrioventricular (AV) discordance and ventriculoarterial concordance. It describes a condition which from a physiological point of view resembles complete transposition of the great arteries. We have recently seen two patients with this anomaly. Both underwent intracardiac repair by means of a Mustard operation at 10 years and 10 months of age, respectively. Associated lesions in the first patient were an AV septal defect with two AV orifices (partial AV canal, ostium primum defect), partial anomalous pulmonary venous return, and anomalies in the systemic venous drainage. A perimembranous ventricular septal defect complicated the condition in the second patient.     

Lumbar disc syndrome in Finland.

The prevalence of lumbar disc syndrome (herniated disc or typical sciatica) and its consequences in terms of disability, handicap, and need for medical care were studied as part of the Mini-Finland Health Survey. A sample of 8000 persons representative of the Finnish population aged 30 or over was asked to come for examination, and 7217 (90%) participated. A diagnosis of lumbar disc syndrome based on medical history, symptoms, and standardised physical examination was made for 5.1% of the men and for 3.7% of the women. Half of these patients were assessed to be in need of medical care, over 80% of which was considered to be adequately met. One third of all patients with lumbar disc syndrome had been previously hospitalised for that syndrome, and one fifth of the patients had undergone lumbar surgery. At least slight disability was found in almost 60% of the patients, though severe functional limitations were rare. About 6% of the population's work disability was estimated to be attributable to lumbar disc syndrome.     

Lymph Node Dissection Impact on Staging and Survival of Extrahepatic Cholangiocarcinomas,Based on U.S. Population Data

Cholangiocarcinomas (CC) frequently demonstrate lymphatic spread. We investigated lymph node (LN) counts after resection of extrahepatic CC and survival based on the SEER 1973–2004 database. Out of 20,068 CC patients, 1,518 individuals were selected based on M0 stage and at least one LN examined. Primary cancer sites included gallbladder (29%), extrahepatic bile ducts (26%), and intrapancreatic/ampullary bile ducts (45%); 42% of patients were LN-positive. The median number of LNs examined was four (range 1–39). Median survival was 37 months for LN-negative and 16 months for LN-positive cancers. Multivariate prognostic variables were the number of positive LNs, primary site, age (all at p < 0.0001), gender (p = 0.002), size (p = 0.005), T category (p = 0.009), and total LN count (or number of negative LNs obtained, p = 0.01). The impact of total LN counts was seen in LN-negative (median survival, 1 vs 10 or more LNs examined: 27 vs 51 months, p = 0.002) and LN-positive disease (10 vs 22 months, p < 0.0001). Survival prediction of extrahepatic CCs is strongly influenced by total LN counts and numbers of negative LNs obtained. Although the resulting incremental benefit is small, dissection and examination of 10 or more LNs should be considered for curative intent resections.     

The impact of peripartum factors on the onset and duration of lactation

Knowledge of peripartum indicators of those mother-infant pairs that are at increased risk of early failure of lactation may improve specific support of breastfeeding. Mode of delivery, labor complications, hyperbilirubinemia, milk intake and weight development were evaluated in healthy term infants in a hospital (n = 338). Delayed onset of lactation was observed in primiparae and in study participants with peripartum complications. The quantitative intake of human milk, assessed by test weighing 0-24 h and 24-48 h after the onset of lactation, was not significantly different between these groups. In addition, volume intake, weight gain and lactation success were tracked in 77 infants. Partial feeding of infant formula or an intake of <150 g of human milk per day 24-48 h after the onset of lactation was linked to weaning within 4 weeks. Ninety-one percent of the infants were exclusively breastfed at discharge; this value had declined to 49, 35 and 20% at 4, 12 and 20 weeks, respectively. Peripartum factors may contribute to early lactation failure; the long-term success of breastfeeding was predominantly determined outside the hospital.     

Hemodynamic performance following the Ross operation: comparison of two different techniques

BACKGROUND AND AIM OF THE STUDY: The Ross operation as aortic valve replacement has undergone technical evolution. Originally described as a subcoronary implant, the full-root replacement technique is now more common worldwide. It remains unclear which of the two techniques has the better results. Hence, the hemodynamic performances of the two implantation methods, as applied by two experienced centers, were compared as part of the German Ross Registry. METHODS: In total, 132 (Group 1, root replacement, mean age 40 +/- 14 years) and 249 (Group 2, subcoronary implant, mean age 48 +/- 14 years) consecutively operated patients were compared clinically and echocardiographically. Data were analyzed focusing on pulmonary autograft and homograft function at mid-term (2.78 +/- 1.89 versus 2.26 +/- 2.11 years). RESULTS: Echocardiography revealed autograft peak systolic gradients of 5.0 +/- 2.7 mmHg for Group 1 and 6.7 +/- 3.7 mmHg for Group 2 (p < 0.05), and an indexed effective orifice area (EOA) of 1.98 +/- 0.57 cm2/m2 and 1.64 +/- 0.43 cm2/m2 (p < 0.05), respectively. Homograft peak systolic gradients were 15.6 +/- 9.0 mmHg and 11.7 +/- 6.8 mmHg for Groups 1 and 2 (p < 0.05) respectively, and the indexed EOA with regard to the homograft was 1.08 +/- 0.49 cm2/m2 and 1.26 +/- 0.50 cm2/m2 (p < 0.05). Autograft insufficiency grade > I was present in 1.5% (2/132) of Group 1 and 2.8% (7/249) of Group 2 patients. Pulmonary insufficiency grade > I was 17.4% (23/132) for Group 1 and 4.8% (12/249) for Group 2 (p < 0.05). CONCLUSION: Although both groups enjoyed excellent hemodynamics in the mid-term, the root replacement technique had the advantage of larger annulus diameters and greater aortic EOA. Clinically relevant autograft regurgitation in both groups was gratifyingly rare, and seemed to be independent of surgical technique. Long-term durability of the more demanding subcoronary technique versus the problems of larger dimensions of the sinus of Valsalva and sinotubular junction in the free-root technique, remains to be proven. Apparent differences in pulmonary homograft hemodynamics can most likely be explained by surgical differences, younger patients in Group 1, and by homograft variation.     

Long-Range, pH-Dependent Effects on the Carbon-13 Nuclear Magnetic Resonance Spectra of Oxytocin

The effects of hydrogen ion concentrations on the carbon-13 nuclear magnetic resonance spectra of oxytocin were investigated. The starting pD of 3.0 was increased stepwise to 8.4. A change of the state of protonation of the N-terminal amino group of oxytocin is accompanied by changes in chemical shifts of carbon-13 nuclei of amino-acid residues located in the 20-membered ring of the hormone. The resonance positions of the acyclic peptide portion, Pro-Leu-Gly-NH(2), remain constant. The pD-induced chemical-shift changes of carbons up to five bonds removed from the site of protonation are interpreted in terms of "through-bond" and "through-space" mechanisms. Chemical-shift changes of carbons more than five bonds removed are proposed to have a conformational origin. It is suggested that a change in the charge density of the amino group perturbs the dihedral angle of the -CH(2)-S-S-CH(2)- moiety of oxytocin, which in turn significantly affects the overall conformation of the 20-membered ring of the hormone.     

Revival of an old method with new techniques: balloon aortic valvuloplasty of the calcified aortic stenosis in the elderly

Balloon aortic valvuloplasty (BAV), introduced since almost 20 years, has experienced a revival for its use in the treatment of elderly patients with severe calcified aortic stenosis that are associated with high operative risk and co-morbidities. This is due to the introduction of new balloon catheters and techniques. This study reports about 75 such cases performed within the past 28 months. The mean age of our patient group was 78 +/- 7 years (median = 80 years). Risk calculation with the EuroSCORE demonstrated an average value of 24.4 +/- 19.5%. BAV was performed along with burst pacing to reduce transvalvular blood flow for stabilization of the balloon catheter until blood pressure dropped to less than 50 mmHg. BAV was performed in 72 patients with a procedural success rate of 73%. There was a decrease of 31 mmHg peak-to-peak gradient across the aortic valve from 63 +/- 35 to 32 +/- 22 mmHg (P < 0.0001). Mean gradient was reduced from 51 +/- 24 to 27 +/- 15 mmHg (P < 0.0001). Aortic valve area increased by 49% from 0.84 +/- 0.33 to 1.25 +/- 0.45 cm(2) (P < 0.0001). Serious adverse events (SAE) occurred in 17% of the 75 BAV procedures. Follow-up revealed a significant improvement in 6-month and 1-year survival. The improved technology of BAV makes this technique attractive for elderly patients who are at high operative risk or in cases where valve replacement was refused for any reason.