Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial

Background

Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes.

Methods

In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration.

Results

In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation.

Conclusion

During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation.

Registration of Clinical Trial

DRKS-ID DRKS00014788 ( www.drks.de ).     

Postoperative management after total hip and knee arthroplasty

Despite major advances in the field of total joint arthroplasty, a standardized postoperative management protocol currently does not exist following total hip arthroplasty (THA) and total knee arthroplasty (TKA). A survey was mailed to the active members of the American Association of Hip and Knee Surgeons to investigate issues such as postoperative rehabilitation and activity restriction. The information derived from this survey provides the total joint surgeon with a compilation and consensus of responses that can serve as the foundation for a standardized postoperative protocol for THA and TKA surgery.     

Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites

Among 404 patients with primary tumors of extremity-trunk sites entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972 to 1984), 154 were placed in clinical group IIa, ie, with negative nodes but with "microscopic residual" (MR) disease, following the initial excisional (not biopsy) procedure. An elective reexcision of the area of the primary tumor (PRE) was performed in 41 of these patients within 35 days (mean interval, 14 days; SE, 0.9) with no intervening therapy. These procedures consisted of wider excision of the tumor "bed," resulting in a technical transfer of these patients from group IIa to group I, ie, complete excision. This reduced intensity of nonsurgical therapy (irradiation and chemotherapy). Among the 41 patients who underwent PRE, the 3-year survival estimate (Kaplan-Meier) was 91% (SE, 4%). This may be compared with the results in 113 patients who remained in group IIa, in which the 3-year survival estimate was 74% (SE, 4%). A second group for comparison consisted of the 73 patients with trunk/extremity tumors who were placed in group I after a single excisional procedure, ie, no PRE, in whom the 3-year survival estimate was 74% (SE, 5%). Recognized prognostic factors influencing survival in these groups were comparable, with the exception of tumor size, ie, the largest tumors (greater than or equal to 10 cm in diameter) were concentrated in groups I and IIa. When patients with tumors greater than or equal to 10 cm in diameter (9.7% of the total) were removed from all three study groups, patients undergoing PRE had longer survival duration estimates than patients in the control groups.     

Revisions to the international guidelines on the diagnosis and therapy of chronic urticaria

At the end of 2012, more than 300 participants discussed and agreed on the update of the international guidelines on urticaria at the 4th International Consensus Meeting (URTICARIA 2012). Currently, the recommendations are in the final process of international coordination. In preparation for the update, questions were prepared by an expert panel; this was followed by a systematic literature search. The questions and the resulting recommendations were discussed by the participants and decided upon in an open vote. Consensus was defined as at least 75% agreement. The updated guidelines will modify and improve the currently available guidelines in various areas, especially in therapy. For the treatment of chronic urticaria, the new algorithm recommends a three‐step process starting with a standard dose of a non‐sedating H1 antihistamine. If there is an insufficient treatment response, the dosage should be increased up to four times. In, therapy refractory patients, omalizumab, cyclosporine A, or montelukast are advised in the third step. Short‐term corticosteroid treatment for a maximum of 10 days may be considered. H2 antihistamines and dapsone, which were included in the previous version of the guidelines, are absent in the updated and revised version because of changes in the evidence level.     

Infection after intramedullary nailing of severe open tibial fractures initially treated with external fixation

Twenty-four patients had a severe open fracture of the tibia that was initially treated by external fixation and subsequently by reamed intramedullary nailing. The external fixation had been maintained for an average of fifty-two days (range, seven to 230 days). The mean interval between removal of the external fixator and intramedullary nailing was sixty-five days (range, three to 360 days). In five of the seven patients who had had an infection at one or more of the pin sites, an infection later developed around the intramedullary nail. In comparison, only one of the seventeen patients who had not had a pin-site infection had an infection later around the nail (p = 0.003). An analysis of other variables, including the duration of external fixation, wound coverage, other injuries, and the type of fracture, showed that none was a predictor of infection either at the pin sites or around the intramedullary nail. We concluded that a pin-site infection that develops during external fixation is a contraindication to the subsequent use of reamed intramedullary nailing in patients who have a fracture of the tibia.     

Approach to the treatment of cutaneous malignancy in HIV-infected patients

Patients infected with human immunodeficiency virus (HIV) have an increased risk of developing skin cancers. These at-risk patients may have atypical presentations and/or altered clinical courses. This article will review and discuss management issues for the following malignancies: lymphomas, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, and Kaposi's sarcoma.     

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.     

Prevalence and predictors of skin disease in the Women's Interagency HIV Study (WIHS)

OBJECTIVE: We attempted to determine the prevalence and predictors of skin disease in a cohort of women with and at risk for HIV infection. METHODS: We analyzed baseline data from a multicenter longitudinal study of HIV infection in women. RESULTS: A total of 2018 HIV-infected women and 557 HIV-uninfected women were included in this analysis. Skin abnormalities were reported more frequently among HIV-infected than uninfected women (63% vs 44%, respectively; odds ratio [OR] 2.10; 95% confidence interval [95% CI], 1.74-2.54). Infected women were also more likely to have more than 2 skin diagnoses (OR, 3.27; 95% CI, 1.31-8.16). Folliculitis, seborrheic dermatitis, herpes zoster, and onychomycosis were more common among HIV-infected women (P < .05). Independent predictors of abnormal findings on skin examination in the infected women were African American race (OR, 1.38; 95% CI, 1.07-1.77), injection drug use (OR, 2.74; 95% CI, 2.11-3.57), CD4(+) count less than 50 (OR, 1.68; 95% CI, 1.17-2.42), and high viral loads (100,000-499,999 = OR, 1.77; 95% CI, 1.32-2.37; > 499,999 = OR, 2.15; 95% CI, 1.42-3.27). CONCLUSION: HIV infection was associated with a greater number of skin abnormalities and with specific dermatologic diagnoses. Skin abnormalities were also more common among women with CD4(+) cell depletion or higher viral load.     

Preservation of products with MCI/MI in Switzerland

Preservation of products with the combination of 5-chloro-2-methyl-4-isothiazolinone (methylchloroisothiazolinone, MCI) and 2-methyl-4-isothiazolinone (methylisothiazolinone, MI), commercialized as Kathon CG or WT, is widely used. Allergic contact dermatitis reactions to the preservative have been described in many publications of epidemiological studies. In addition, a number of allergic, airborne reactions to MCI/MI were observed in recent years. The aim of the presented study was: (i) to compare epidemiological data of MCI/MI with data of other preservatives; (ii) to estimate the possible exposure to MCI/MI from commercial products and the distribution of MCI/MI in chemical products based on a product evaluation of the chemical product register of the Swiss Federal Office of Public Health; (iii) to estimate the exposure to MCI/MI, volatile organic chemicals (VOC) and glycols from freshly painted walls; (iv) to compare the contact allergenic potential of MCI/MI with other preservatives. It was found that the number of registered chemical products, unambiguously identifiable as containing MCI increased from 3644 products in July 1999 to 4843 products in April 2001 in Switzerland. It is estimated that today, the total number of chemical products preserved with MCI/MI on the Swiss market is about 6000. A further increase is to be expected. The contact allergenic potential of MCI/MI seems to be higher than for other preservatives. Measurements of MCI/MI concentrations in air samples of freshly painted rooms have shown that the concentration of MCI/MI in the air a few days after painting may be high enough to elicit airborne reactions in already-sensitized patients. In a single case, reactions to MCI/MI were observed over months after wall painting. In this case, both wall paint and plaster contained MCI (40 and 46 ppm). Volatile organic chemicals (VOC) may also be relevant for the elicitation of airborne reactions. In 1/3 of the measurements, the VOC concentrations measured within 14 days after painting were in a range within which sensory irritation and discomfort may be induced. Declaration of MCI/MI-containing products, replacement of MCI/MI by alternative preservatives or the separate use of preservatives in industrial products and in cosmetics might reduce the risk of airborne reactions.