Plasma lidocaine concentrations after local anesthesia of the groin for cardiac catheterization.

This study aimed to investigate serum lidocaine concentrations after subcutaneous infiltration of the groin for cardiac catheterization. One hundred twenty-six patients for planned heart catheterization received five different dosages (5-25 ml) of lidocaine 2% for local anesthesia of the groin in a randomized manner. All of them received an arterial sheath and 13 received both an arterial sheath and a venous sheath for right heart catheterization. Blood samples were taken before as well as 15, 30, and 120 min after subcutaneous application of the drug. Although in 33 patients with an arterial sheath (no venous sheath) excessive doses of lidocaine 2% (20-25 ml) were used, neither symptoms of intoxication nor toxic plasma levels were observed. However, in patients receiving an additional venous sheath, toxic plasma levels were obtained in a third of the cases. One of them showed symptoms of intoxication.     

Efficacy of anterior odontoid screw fixation in the elderly patient: a CT-based biometrical analysis of odontoid fractures

In the elderly population, reported union rates with anterior odontoid screw fixation (AOSF) for odontoid fracture (OF) treatment vary between 23 and 93% when using plain radiographs. However, recent research revealed poor interobserver reliability for fusion assessment using plain radiographs compared to CT scans. Therefore, union rates in patients aged ≥60 years treated with AOSF have to be revisited using CT scans and factors for non-union to be analysed. Prospectively gathered consecutively treated patients using AOSF for odontoid fracture with age ≥60 years were reviewed. Medical charts were assessed for demographics, clinical outcomes and complications. Patients’ preoperative radiographs and CT scans were analysed to characterize fracture morphology and type, fracture displacement, presence of atlanto-dental osteoarthritis as well as a detailed morphometric assessment of fracture surfaces (in mm²). CT scans performed after a minimum of 3 months postoperatively were analysed for fracture union. Those patients not showing CT-based evidence of completely fused odontoid fracture were invited for radiographic follow-up at a minimum of 6 months follow-up. Follow-up CT-scan were studied for odontoid union as well as the number of screws used and the square surface of screws used for AOSF and the related corticocancellous osseous healing surface of the odontoid fragment (in %) were calculated. Patients were stratified whether they achieved osseous union or fibrous non-union. Patients with a non-union were subjected to flexion–extension lateral radiographs and the non-union defined as stable if no motion was detected. The sample included 13 male (72%) and 5 female (18%) patients. The interval from injury to AOSF was 4.1 ± 5.3 days (0–16 days). Age at injury was 78.1 ± 7.6 years (60–87 years) and follow-up was 75.7 ± 50.8 months (4.2–150.2 months). 10 patients had dislocated fractures, 14 had Type II and 4 “shallow” Type III fractures according to the Anderson classification, 2 had stable C1-ring fractures, 8 had displayed atlanto-dental osteoarthritis. Fracture square surface was 127.1 ± 50.9 mm² (56.3–215.9 mm²) and osseous healing surface was 84.0 ± 6.8% (67.6–91.1%). CT-based analysis revealed osseous union in 9 (50%) and non-union in 9 patients (50%). Union rates correlated with increased fracture surface (P = 0.02). Statistical analysis revealed a trend that the usage of two screws with AOSF correlates with increased fusion rates (P = 0.06). Stability at C1–2 was achieved in 89% of patients. CT scans are accepted as the standard of reference to assess osseous union. The current study offers an objective insight into the union rates of odontoid fractures treated with AOSF using CT scans in consecutive series of 18 patients ≥60 years. Literature serves evidence that elderly patients with unstable OF benefit from early surgical stabilization. However, although using AOSF for unstable OF yields segmental stability at C1–2 in a high number of patients as echoed in the current study, our analysis stressed that using follow-up CT scans in comparison to biplanar radiographs dramatically reduces osseous union rates compared to those previously reported for AOSF.     

Controversies and open questions in the definitions and classification of the hypereosinophilic syndromes and eosinophilic leukemias

Eosinophilia is frequently detectable in certain myeloid neoplasms and various reactive conditions, but it may also occur in the absence of an apparent underlying disease, or, rarely, as a paraneoplastic feature with solid tumors. In myeloid neoplasms, eosinophils are considered to belong to the malignant clone in most cases, whereas in all other conditions, eosinophilia is a reactive process triggered by eosinopoietic cytokines. Excessive accumulation of eosinophils, also termed hypereosinophilia (HE), is typically seen in eosinophilic leukemias, but it may also occur in other neoplasms and reactive disorders. HE-related end organ damage may develop in patients with reactive HE but also in those with hematologic malignancies. During the past few years, our knowledge about HE and HE-related organ damage in hematologic and nonhematologic disorders has improved considerably. Moreover, proposals for the definition and classification of eosinophil disorders have been generated by various expert groups and by the World Health Organization (WHO). However, several questions related to eosinophils and HE remain open, and many aspects of the definition and classification of eosinophil disorders and related pathologies remain controversial. In the current article, these open issues are discussed with special reference to the 2008 WHO classification of myeloid neoplasms and other classifications proposed by immunologists and various expert panels, as well as definitions and criteria recently proposed in a multidisciplinary consensus proposal.     

Voiding and sexual dysfunction after deep rectal resection and total mesorectal excision

OBJECTIVE: Voiding and sexual dysfunction after deep rectal resection have been described with various frequencies in the literature. In this study, we prospectively evaluated the baseline preoperative voiding and sexual function in a cohort of patients undergoing deep rectal resection with mesorectal excision to determine any pre-existing abnormalities. Postoperatively, we sought first to determine the frequency of a urinary or sexual dysfunction, secondly whether there is a time-dependent change of a dysfunction and thirdly whether there is a relationship between postoperative urological dysfunction and the patient's age. PATIENTS AND METHODS: Fifty-two patients (36 men and 16 women) with a primary rectal carcinoma were prospectively examined directly before and after the operation, as well after the third and sixth postoperative month. The preoperative urological evaluation consisted of a careful voiding and sexual history, uroflowmetry and a sonographic residual urine determination. A detailed sexual history was obtained via the use of a questionnaire. RESULTS: Urological dysfunction: Preoperatively, 49 of the 52 patients had a completely normal bladder function and three patients had post void residual >100 ml. Postoperatively, 12 of the 49 patients with normal preoperatively urinary function had voiding dysfunction, but only four male patients had residual urine in the third postoperative month. Therefore, in about 90% of the patients, postoperative bladder function became normal and only 10% suffered from vesical denervation after 6 months. We could not determine a relationship between the degree of bladder dysfunction and the patient's age due to a relatively small patient cohort in this study. Sexual dysfunction: Preoperatively, 36 (seven women, 29 men) of the 52 patients were potent and had regular sexual intercourse. Eleven men specified a limited erection, but all had occasional sexual intercourse. One of the potent men experienced no ejaculation. Postoperatively, eight of the 29 men were impotent and two of the 29 men experienced retrograde ejaculation. Therefore, 30% of the preoperatively potent men had sexual dysfunction postoperatively. There was no correlation between the postoperative impotence and the age of the patients at the time of surgery. Although it is likely that the potency may diminish with advanced age, the incidence of impotence was not higher in the older patients of our study. CONCLUSIONS: The results of our study underline the importance of risk estimation for possible postoperative urological dysfunction by means of preoperative urologic evaluation in this patient collective. Of patients with postoperative bladder dysfunction, 90% improved within 6 months after surgery and only 10% continued to have bladder dysfunction beyond 6 months, indicating irreversible nerve damage.     

Survival of the fittest: in vivo selection and stem cell gene therapy

Stem cell gene therapy has long been limited by low gene transfer efficiency to hematopoietic stem cells. Recent years have witnessed clinical success in select diseases such as X-linked severe combined immunodeficiency (SCID) and ADA deficiency. Arguably, the single most important factor responsible for the increased efficacy of these recent protocols is the fact that the genetic correction provided a selective in vivo survival advantage. Since, for most diseases, there will be no selective advantage of gene-corrected cells, there has been a significant effort to arm vectors with a survival advantage. Two-gene vectors can be used to introduce the therapeutic gene and a selectable marker gene. Efficient in vivo selection strategies have been demonstrated in clinically relevant large-animal models. Mutant forms of the DNA repair-enzyme methylguanine methyltransferase in particular have allowed for efficient in vivo selection and have achieved sustained marking with virtually 100% gene-modified cells in large animals, and with clinically acceptable toxicity. Translation of these strategies to the clinical setting is imminent. Here, we review how in vivo selection strategies can be used to make stem cell gene therapy applicable to the treatment of a wider scope of genetic diseases and patients.     

Differential responses of FLIPLong and FLIPShort-overexpressing human myeloid leukemia cells to TNF-alpha and TRAIL-initiated apoptotic signals

OBJECTIVE: Clonal marrow cells from patients with early myelodysplastic syndrome (MDS) undergo apoptosis in response to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Cells from advanced MDS are resistant to TRAIL. Two isoforms of the Flice inhibitory protein (FLIP) short (FLIPS) and FLIP long (FLIPL), which modulate TRAIL signals, showed disease-stage-dependent differential regulation. Therefore, we aimed at characterizing potential differential effects of FLIPL and FLIPS, on TRAIL and TNF-alpha-induced apoptosis in model leukemic cell lines. MATERIALS AND METHODS: Using lentiviral constructs, FLIPL and FLIPS, as well as a green fluorescent protein control were overexpressed in ML-1 cells, which constitutively express very low levels of FLIP and are highly sensitive to apoptosis induction. Cells were then exposed to TRAIL or TNF-alpha, and effects on the extrinsic and intrinsic pathways of apoptosis induction were assessed. RESULTS: Overexpression of FLIP reduced TRAIL and TNF-alpha-induced apoptosis in ML-1 cells. However, while FLIPL completely abrogated apoptosis, FLIPS allowed for BID cleavage and caspase-3 activation. Concurrently, there was a decline of Bcl-xL and X-linked inhibitor of apoptosis protein (XIAP) in FLIPS cells followed by apoptosis. Further, inhibition of nuclear factor-kappaB (NF-kappaB) activation in TNF-alpha-treated cells resulted in profound apoptosis in FLIPS, but not in FLIPL-overexpressing cells, consistent with the observations in patients with early stage MDS. Inhibition of NF-kappaB had only minimal effects on TRAIL signaling. CONCLUSION: Thus, FLIPL and FLIPS exerted differential effects in myeloid leukemic cell lines in response to TRAIL and TNF-alpha. It might be possible to therapeutically exploit those differences with effector molecules specific for the FLIP isoforms.     

Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology

Cytokines released by infiltrating T cells may contribute to the hepatic injury in chronic hepatitis. Therefore, we characterized peripheral blood- and liver-infiltrating T cells from patients with chronic hepatitis of different etiology and determined the T cell phenotypes and the cytokine release. Liver tissue and peripheral blood-derived T cells from patients with autoimmune hepatitis and primary biliary cirrhosis predominantly expressed CD4-molecules and the α- and β-chains of the T cell receptor (TCR). In chronic viral hepatitis B and C, liver- and blood-derived T cells were preferentially CD8+ T cells expressing the αβ TCR. Mitogenic stimulation with irradiated Daudi lymphoma cells and phytohemagglutinin led to a strong release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) by T cells in patients with chronic hepatitis and in healthy controls. T cells from patients with primary biliary cirrhosis and some patients with autoimmune hepatitis showed a significantly higher secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10) than T cells from patients with chronic viral hepatitis or healthy controls. Histologic inflammatory activity did not correlate with the amount of cytokines released after mitogenic activation. In conclusion, liver tissue and peripheral blood T cells of patients with autoimmune hepatitis and primary biliary cirrhosis were dominated by CD4+ TCR αβ+ T helper/inducer cells, whereas in chronic viral hepatitis an enrichment of CD8+ TCR αβ+ cytotoxic/suppressor T cells was observed. In addition, analysis of the cytokine release showed that T cells in autoimmune and chronic viral liver diseases secreted high amounts of IFN-γ and TNF-α, cytokines predominantly secreted by T_hl-like cells. The secretion of the T_h2 cytokines. IL-4 and IL-10, however, was increased in autoimmune hepatitis and primary biliary cirrhosis. These data show that in autoimmune and chronic viral liver diseases different functional T cell subsets are activated.     

Digital versus conventional implant impressions for partially edentulous arches: An evaluation of accuracy

Statement of problem

To the authors’ knowledge, while accuracy outcomes of the TRIOS scanner have been compared with conventional impressions, no available data are available regarding the accuracy of digital scans with the Omnicam and True Definition scanners versus conventional impressions for partially edentulous arches.

Prospective comparison of contrast enhanced CT colonography and conventional colonoscopy for detection of colorectal neoplasms in a single institutional study using second-look colonoscopy with discrepant results

BACKGROUND: Colorectal cancer is the second leading cause of death from cancer in Western countries. Early detection by colorectal cancer screening can effectively cut its mortality rate. CT colonography represents a promising, minimally invasive alternative to conventional methods of colorectal carcinoma screening. AIMS: The purpose of this prospective single institutional study was to compare the abilities of routine clinical CT colonography and conventional colonoscopy to detect colorectal neoplasms using second-look colonoscopy to clarify discrepant results. PATIENTS AND METHODS: CT colonography was performed in 100 symptomatic patients using contrast enhanced multidetector CT followed by conventional colonoscopy on the same day. If results were discrepant, a second-look colonoscopy was performed after unblinding. CT colonographic findings were compared with those of conventional colonoscopy. RESULTS: Conventional colonoscopy found 122 colorectal neoplasms in 49 patients. The overall sensitivity of CT colonography at detecting patients with at least one polyp 6 mm or larger was 76% and its specificity was 88%. Its by-patient sensitivity for polyps 10 mm or larger was 95% and its specificity was 98%. By-polyp sensitivities were 71% for polyps 10 mm or larger, and 61% for polyps 6 mm or larger. A second-look colonoscopy was performed in 19 patients and two initial false-positive findings of CT colonography were reclassified as true-positive. For conventional colonoscopy, this produced a by-polyp sensitivity of 94% for detection of lesions 6 mm and larger. CONCLUSIONS: CT colonography had both a high by-patient sensitivity and specificity for detection of clinically important colorectal neoplasms 10 mm or larger. This suggests that CT colonography has the potential to become a valuable clinical screening method for colorectal neoplasms.