Development of tyrosine hydroxylase-, dopamine- and dopamine β-hydroxylase-immunoreactive neurons in a teleost, the three-spined stickleback

The development of catecholaminergic neuronal systems in the brain of a teleost, the three-spined stickleback, was studied through embryonic to early larval stages by immunocytochemistry using specific antibodies against dopamine, tyrosine hydroxylase and dopamine β-hydroxylase. By analysing the spatiotemporal patterns of development for the catecholaminergic nuclei, possible homologies with nuclei in amniote brains have been identified.

The noradrenergic neurons in the isthmus region of the rostral rhombencephalon originate in the same manner as the A4–A7 + subcoeruleus group in mammals. Their developmental characteristics show the largest similarities with the subcoeruleus group of birds and mammals, although some features are shared with developing A6 (locus coeruleus) neurons.

Catecholaminergic neurons never appear during development in the ventral mesencephalon of the three-spined stickleback. A group of large dopaminergic neurons that accompany the cerebrospinal fluid (CSF)-contacting neurons follows the border between the hypothalamus and the ventral thalamus into the caudal hypothalamus, where they are continuous with the dopaminergic neurons in the posterior tuberculum. They are thus topologically comparable with the dopaminergic neurons of the zona incerta in mammals.

The dopaminergic CSF-contacting neurons that line the median, lateral and posterior recesses of the third ventricle do not contain tyrosine hydroxylase-immunoreactivity at any developmental stage. This indicates that they take up and accumulate exogenous dopamine or -dihydroxyphenylalanine, and do not synthesize dopamine from tyrosine at any developmental stage. Tyrosine hydroxylase-immunoreactive neurons appear in the pineal organ on the day of hatching (120 h post-fertilization). They were still observed in 240-h-old larvae, but are absent in the pineal organ of adult sticklebacks.

The initial appearance and subsequent differentiation of catecholaminergic neurons in the stickle-back embryo follow essentially the same spatial and temporal pattern as in amphibian, avian and mammalian embryos. This observation supports the hypothesis that morphologically, topologically and chemically similar monoaminergic neurons in different vertebrate classes are homologous.     

Intracellular Reservoir of Streptococcus pyogenes In Vivo: A Possible Explanation for Recurrent Pharyngotonsillitis

Numerous theories have been presented that attempt to explain the frequent recurrences of pharyngotonsillitis caused by Streptococcus pyogenes; these recurrences occur after seemingly adequate antibiotic treatment. We previously have demonstrated that S pyogenes can survive for up to 7 days intracellularly in immortalized human respiratory epithelial cells grown in an antibiotic supplemented medium. Viable S pyogenes were externalized and established an extracellular infection, whenever the extracellular antibiotic was removed. We have investigated the presence of intracellular S pyogenes in two in vivo studies using respiratory epithelial cells collected from patients with tonsillitis and the tonsils of asymptomatic carriers. Electron microscopy and immunohistochemistry demonstrated intracellular S pyogenes in pharyngeal epithelial cells in 13 of 14 patients with tonsillitis (93%). Furthermore, intracellular S pyogenes were found in macrophage-like cells in eight (73%) and in epithelial cells in four (36%) tonsils from 11 asymptomatic S pyogenes carriers. These in vivo data strongly support the hypothesis that intracellular S pyogenes can constitute a reservoir of bacteria with the potential to cause reinfections     

Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk

An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR) = 0.8, 95% confidence interval (CI) = 0.5-1.1) nor for latent antibodies (RR = 0.6, 95% CI = 0.1-2.7). Similar risks were seen when analysis was restricted to case-control sets with at least 2 years lag before diagnosis (RR = 0.8, 95% CI = 0.5-1.2 and RR = 0.9, 95% CI = 0.1-4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM.     

Laparoscopic sigmoid and rectal resection using an electrothermal bipolar vessel sealing device

BACKGROUND: Laparoscopic colonic resection has gained popularity as a method to treat colonic diseases. The electrothermal bipolar vessel sealer (EBVS; LigaSure Atlas) is a modern device that allows the secure sealing of vessels with a diameter of up to 7 mm. The aim of the present study was to evaluate the suitability of the device for laparoscopic colonic surgery. METHODS: The immediate outcome of 114 consecutive patients who underwent a sigmoid or rectal resection was prospectively analyzed. The intention was to perform all operations with the EBVS for dissection and ligation of the mesenterial vessels. Details on patient characteristics, peroperative and postoperative complications, and postoperative recovery were recorded prospectively and analyzed. RESULTS: One hundred and fourteen patients were scheduled for elective left-sided colonic or rectal resection. Massive intra-abdominal adhesions in 1 patient required a conversion of the laparoscopic procedure to an open one; In total, 113 laparoscopic operations were thus performed. The mean operative time was 87.7 +/- 2.8 minutes, and the mean time for patients to tolerate solid food was 3.4 +/- 0.1 days and the time to discharge from hospital was 4.6 +/- 0.2 days. There were nine (8.0%) general complications, and additionally, 10.6% of patients suffered from surgical complications. CONCLUSIONS: The electrothermal bipolar vessel sealer is suitable and safe for laparoscopic sigmoid and rectal resections. The use of the device probably reduces the operative time.     

Two-ring hybrid external fixation of distal tibial fractures: a review of 47 cases

BACKGROUND: The healing of a metaphyseal fracture line is a major problem in cases of distal tibial fracture treated with external fixation. METHODS: Forty-seven distal tibial fractures treated with two-ring Ilizarov hybrid external fixation (16 AO/OTA type A and 31 type C, 10 open) were followed up. Fracture reduction and union time was evaluated and IOWA and RAND 36-Item Health Survey scores were used to assess functional outcome. RESULTS: Thirty-five fractures united uneventfully in a median time of 20 weeks, but 12 fractures needed additional procedures because of delayed union. According to univariate analysis, the risk factors for a longer time needed for fracture union were translational displacement and current smoking, and the risk factors for reoperation because of delayed union translational displacement fibular fracture fixation, and the number of cigarettes smoked per day. In multivariate analysis, translational displacement was a risk factor for both longer time to fracture union and reoperation and fibular fracture fixation was a risk factor for reoperation. If the translational displacement was less than 3 mm, the reoperation rate was 6%, whereas if the displacement was more than 3 mm, it was 83%. Reoperation was performed on 50% of the patients who underwent fibular fixation and on 15% of the patients who did not undergo fibular fixation. There were only marginal decreases in the range of motion and arthritis scores in the AO/OTA fracture types other than type C3. There were no significant differences in RAND 36 scores between the general Finnish population aged 18 to 64 years and our patients. CONCLUSIONS: Hybrid external fixation of distal tibial fractures is associated with delayed union, which is closely related to the degree of residual translational displacement after reduction. Fixation of an associated fibular fracture does not help to achieve better contact in the tibial fracture and increases the risk of delayed union.     

Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents

This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40–80-year-old NL received positron emission tomography (PET) with ¹¹C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ −0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9–5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD.     

Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer.METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as “front-positive” and in 41% as “front-negative”. The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the “front-positive” tumors.CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.