Cobalamin: a critical vitamin in the elderly

Vitamin B(12) deficiency is a common problem in elderly subjects. If a serum cobalamin level of about 150 pmol/L (200 pg/mL) is considered normal, 10-15% of the elderly are deficient. Today, however, a threshold of 220-258 pmol/L (300-350 pg/mL) is recognized as desirable in the elderly, or else sensitive markers like the blood concentration of homocysteine or methylmalonic acid (MMA) are used. Then the prevalence of cobalamin deficiency rises to up to 43%. In the elderly, this high prevalence of poor cobalamin status is predominantly caused by atrophic gastritis type B. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal absorption of the cobalamin protein complexes from food. About 20-50% of the elderly are affected. Furthermore, the reduced acid secretion leads to an alkalinization of the small intestine, which may result in bacterial overgrowth and thus to a further decrease of the bioavailability of the vitamin. In addition, some drugs such as proton pump inhibitors or H2 receptor antagonists inhibit the intestinal absorption of vitamin B(12). An already moderately reduced vitamin B(12) level is associated with vascular disease and neurocognitive disorders such as depression and impaired cognitive performance. Furthermore, a poor vitamin B(12) status is assumed to be involved in the development and progression of dementia (e.g., Alzheimer's dementia). This is especially observable if the folic acid status is reduced as well. Due to the insecure supply, the cobalamin status of elderly persons (>/=60 years) should be regularly controlled and a general supplementation with vitamin B(12) (>50 microg/day) should be considered.     

Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are extremely rare before age 40 years. The objective of the current study was to determine whether the features of PDACs in patients age < 40 years differ from those in older patients. The authors reviewed the literature and their own files. METHODS: The cases reported in the literature were evaluated to determine their precise diagnoses and characteristic features. In a series of 439 PDACs from the authors' files, tumors in patients age < 40 years were identified, and their clinicopathologic features and certain genetic features were compared with those in a selected group of patients age > 40 years. RESULTS: Of 71 pancreatic carcinomas reported in patients age < 40 years, only 20 fully qualified as PDACs. The remaining tumors represented malignancies other than PDACs, such as pancreatoblastoma, solid-pseudopapillary neoplasms, acinar cell carcinomas, and endocrine tumors. PDACs in patients age < 20 years were the absolute exception and commonly were associated with risk factors such as Peutz-Jeghers syndrome, hereditary pancreatic cancer syndrome, and preceding radiotherapy. In the authors' series of patients, there were 6 PDACs and 4 PDAC variants in patients age < 40 years (0.2%), all in male patients. These tumors compared well with the PDACs in patients age > 40 years in their pathologic and molecular findings. Three patients were age < or = 20 years, and 2 of those patients had a mucinous component with MUC2 positivity. CONCLUSIONS: The incidence of PDACs in patients age < 40 years was approximately 0.3%, and the incidence in patients age < 20 years was 0.1%. Their clinicopathologic findings were comparable to those in patients age > 40 years, but they seemed to include more variants, particularly mucinous carcinomas. In addition, PDACs in younger patients frequently appeared to be associated with genetic factors.     

The effects of chronic intracochlear electrical stimulation on inferior colliculus spatial representation in adult deafened cats

Previous studies have shown that chronic electrical stimulation through a cochlear implant causes significant alterations in the central auditory system of neonatally deafened cats. The goal of this study was to investigate the effects of chronic stimulation in the mature auditory system. Normal hearing adult animals were deafened by ototoxic drugs and received daily electrical stimulation over periods of 4-6 months. In terminal physiology experiments, response thresholds to pulsatile and sinusoidal signals were recorded within the inferior colliculus (IC). Using previously established methods, spatial tuning curves (STCs; threshold vs. IC depth functions) were constructed, and their widths measured to infer spatial selectivity. The IC spatial representations were similar for pulsatile and sinusoidal stimulation when phase duration was taken into consideration. However, sinusoidal signals consistently elicited much lower thresholds than pulsatile signals, a difference not solely attributable to differences in charge/phase. The average STC width was significantly broader in the adult deafened/stimulated animals than in controls (adult deafened/unstimulated cats), suggesting that electrical stimulation can induce spatial expansion of the IC representation of the chronically stimulated cochlear sector. Further, results in these adult animals were not significantly different from results in neonatally deafened, early stimulated animals, suggesting that a similar degree of plasticity was induced within the auditory midbrains of mature animals.     

Developmental and subcellular effects of chronic exposure to sub-lethal concentrations of ammonia,PAH and PCP mixtures in brown trout (Salmo trutta f. fario L.) early life stages

Brown trout (Salmo trutta f. fario L.) early life stages were studied for physiological effects caused by chronic exposure to sub-acute levels of unionised ammonia, a mixture of PCP and PAHs, and a combination of ammonia and the mixture of organics during the entire embryonic development. Nominal concentrations of tested compounds were based on field data. Accumulation data for PAHs and PCP in trout tissue reflected respective water concentrations of PCP and PAHs. Physiological responses were studied by early life stage tests (ELST) and by the analysis of the 70 kDa stress protein (hsp70). Endpoint responses in the ELST were: accelerated development, pre-hatching, and increased heart rates. For these endpoints, response levels were highest in the ammonia treatment, followed by the exposure to the PCP/PAH mixture. Weight was reduced in embryos treated with the PCP/PAH mixture, but not in the group treated with this mixture combined with ammonia. Induction of hsp70 by the test agents was found to be stage-specific with increased response levels at advanced developmental stages. In both the ELST and hsp70 analysis, response levels were lower in the combined ammonia/PCP/PAH treatment than in groups treated with either ammonia or the PCP/PAH mixture alone.     

Langerhans' cell histiocytosis with bilateral temporal bone involvement

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a rare disease with variable clinical appearance. The etiology of LCH remains unclear to date. It is currently believed that clonal accumulation and proliferation of CD1a-positive Langerhans' cells are causative. METHODS: A 2-year-old boy presented with hypacusis and disturbance of balance. Auditory brainstem-evoked responses (ABRs) revealed severe bilateral labyrinthine hearing loss. Magnetic resonance imaging (MRI) showed inflammatory changes with bone erosion in both temporal bones including labyrinthine systems and mastoid processes. RESULTS: During bilateral surgical exploration, fragile slightly yellowish tissue with necrotic areas was found that turned out to be LCH on histology. Chemotherapy with vinblastine and prednisone was subsequently initiated, leading to continuing complete remission. CONCLUSIONS: The initial presentation of LCH with bilateral temporal bone involvement is a very rare condition. The signs and symptoms of otologic histiocytosis can mimic those of acute and chronic infectious ear disease. Only a surgically obtained biopsy leads to definitive diagnosis and appropriate therapy.     

Propofol versus midazolam for procedural sedation in the emergency department: A study on efficacy and safety

Background

Procedural sedation for painful procedures in the emergency department (ED) can be accomplished with various pharmacological agents. The choice of the sedative used is highly dependent on procedure- and patient characteristics and on personal- or local preferences.

Phase-variable Expression of Lipopolysaccharide Contributes to the Virulence of Legionella pneumophila

The mechanisms that maintain memory in T cells are not completely understood. We have investigated the role of antigen and interleukin (IL)-2 in the growth and maintenance of CD8⁺ T cells using a cytolytic T cell line specific for ovalbumin (OVA)_257-264 presented by H-2K^b. This line does not secrete IL-4 or IL-2; hence, stimulation with the OVA-transfected EL4 line (E.G7-OVA) does not induce proliferation without addition of exogenous growth factors. Furthermore, this line can be maintained continuously by weekly addition of irradiated, splenic filler cells and IL-2, with or without E.G7-OVA. Although IL-2 induced proliferation of these cytotoxic T lymphocytes (CTLs), production of interferon γ and tumor necrosis factor α required stimulation of the CTL with E.G7-OVA. The kinetics of lymphokine secretion after stimulation by E.G7-OVA were the same whether the CTL had been maintained with or without antigen (Ag). In addition, both CTL lines killed E.G7-OVA target cells within 4 h. Thus, the effector functions of these CTLs were rapidly induced by T cell receptor (TCR) occupancy. CTLs cultured with or without Ag also served as memory T cells when parked for 100 d in unirradiated, syngeneic recipients without OVA. In the absence of OVA, the precursor frequency was identical in spleens of normal and β₂-microglobulin knockout recipients, but significantly less in IL-2 knockout mice. The decline of memory in the absence of IL-2 supports data from other investigators, suggesting that cell cycling is important to the maintenance of CD8⁺ T cell memory. These data also suggest that stimulation of OVA-specific CTLs by lymphokines seems to be more important to maintaining memory than stimulation of TCRs by cross-reactive peptides complexed to class I molecules.Memory is a hallmark of the immune response to T cell–dependent antigens. Memory, in both B and T cells, is manifest by stronger and quicker responses upon secondary exposure to antigen. The mechanisms that maintain memory are not completely understood. In part, T cell memory reflects an increase in the frequency of precursor cells. Memory T cells are also qualitatively distinct from naive T cells in that they have less stringent requirements for activation and respond more rapidly than naive T cells (for review see reference 1). Naive and memory T cells are distinct from effector T cells in that the latter are actively engaged in lymphokine secretion and lytic function in the case of CD8⁺ T cells. By contrast, both naive and memory T cells must be stimulated with antigen to express these effector functions. Naive T cells can be distinguished from effector T cells by differences in the expression of several cell-surface antigens. However, effector T cells cannot be easily distinguished from memory T cells because they both express activation antigens and increased density of adhesion molecules.Several important questions remain concerning the maintenance of memory T cells. The question of whether antigen is required for memory T cell persistence has been the subject of considerable debate. The majority of studies on the requirement for antigen in maintaining CD8⁺ memory T cells have been performed using polyclonal T cells activated by viruses such as lymphocytic choriomeningitis virus (LCMV), Sendai virus, or influenza. One of the major obstacles in studying memory in virus-specific, CD8⁺ T cells is ruling out restimulation by persisting Ags. However, transfer of CD8⁺ T cells from infected mice into irradiated, syngeneic recipients showed that memory persisted in the absence of virus, as measured by PCR (2–4). Another important issue is the relationship between effector and memory T cells. Whether memory T cells are derived from effector T cells in a linear fashion or whether they differentiate along separate pathways is not known. Signals that regulate development of memory T cells have not been identified.We have recently demonstrated that soluble OVA emulsified in CFA (5) or nonionic block copolymer adjuvants primed CD8⁺ CTL precursors in mice (6). These OVA-specific CTLs (OVA-CTLs) produced IFN-γ and TNF-α upon stimulation with E.G7-OVA or with OVA_257-264 in association with H-2K^b (6). However, these OVA-CTL cells do not produce IL-2 or -4. We reasoned that such CD8⁺ T cells would provide a good model for studying the memory function of CTLs because persistence of Ags would not be a problem. The results presented below compare the requirements for activation of CTLs versus maintenance of memory CTLs in vitro and in vivo. Our results show that CD8⁺ CTLs specific for the exogenous Ag, OVA, have the same potential to persist as memory T cells specific for viruses and tumors. Moreover, persistence of memory T cells was more dependent upon IL-2 than cross-reactive complexes of peptides and MHC class I antigens.     

Comparison of microarray-based RNA expression with ELISA-based protein determination of HER2, uPA and PAI-1 in tumour tissue of patients with breast cancer and relation to outcome

Purpose  

Prognostic and predictive markers in breast cancer are currently determined by single analysis of protein amounts. If RNA-based multi-gene analyses enter clinical practice, simultaneous determination of currently established markers like human epidermal growth factor receptor 2 (HER2), urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) would represent an elegant simplification. To investigate the correlation between RNA and protein levels, we assessed HER2, uPA and PAI-1 in patients with breast cancer. In addition, we evaluated the influence of these factors on patient outcome.