Intraoperative Evaluation von komplexen Mitralklappenrekonstruktionen durch physiologische Provokationstests

Objective

Based on experimental data it was tested, whether intraoperatively performed physiological provocation tests – in addition to morphological information – can improve the quality of complex mitral valve repair (CMVR).

Methods

The quality of CMVR (n=95) was routinely evaluated by transesophageal echocardiography. Shortly before weaning from ECC (flow: 1,5 l/min) the force frequency relation (tested by epimyocardial pacing, frequency range: 80-150 beats per minute), the Frank Starling mechanism (right atrial loading between 2-18 mmHg) and afterload dependency (systolic pressure: 70-140 mmHg) were analysed. Whenever significant mitral valve incompetence (MVI)>1.5 was detected, a surgical re-evaluation was carried out.

Results

Using these procedures, MVI>1.5, which was not observed using steady-state conditions, was detected in 19 patients. In 14 patients, the subsequently performed second repair was successful. In 5 patients the second reconstruction failed again and mitral valve replacement was performed, although neither intraoperative evaluation with saline solution nor standard echocardiography revealed MVI>1.5. In all patients the force frequency was most sensitive to detect functional problems of CMVR (n=18). Afterload alteration (n=12) and preload alteration (n=5) were less sensitive. Postoperatively MI was 0-5 in 70 pts, 0.5-1 in 20, and 1-1.5 in 5 pts.

Conclusion

The data suggest that intraoperatively performed physiological tests, especially the force frequency relation, are important tools to evaluate the myocardial component of mitral valve performance. A pathologically altered dependency on preload, afterload and frequency of mitral valve function can be easily detected by this method.     

Angiotensin receptor antagonist vs. angiotensin-converting enzyme inhibitor in Asian subjects with type 2 diabetes and albuminuria - a randomized crossover study

BACKGROUND: Subjects with type 2 diabetes mellitus (T2DM) and albuminuria are at risk for progressive diabetic nephropathy. The relative blood pressure lowering and antialbuminuric efficacy of angiotensin receptor antagonist (ARB) vs. angiotensin-converting enzyme (ACE) inhibitor has not been well studied. METHODS: Forty-one ARB- and ACE inhibitor-naive T2DM subjects with albuminuria (>30 mg/g creatinine) were given either 50 mg of losartan (ARB) or 20 mg of quinapril (ACE inhibitor) (50% maximum dose) for 4 weeks, with a 4-week wash-out period in-between interventions in a crossover fashion. The order of intervention was randomized. The primary endpoint was the reduction of blood pressure and albuminuria. Secondary endpoint was changes in plasma transforming growth factor beta (TGF-beta). RESULTS: Among the 41 subjects, 66% were male. The mean age (s.d.) was 52 (10) years, and duration of diabetes was 8 (14) years. Blood pressure reduction (though not statistically significant) was similar on both interventions [systolic: losartan 3 (15) vs. quinapril 2 (13) mmHg, p = 0.52; diastolic: losartan 1 (9) vs. quinapril 2 (8) mmHg, p = 0.55]. However, amelioration of albuminuria [mean (s.e.)] was significantly greater with losartan [losartan vs. quinapril: -93 (82) vs. -49 (65) mg/g, p = 0.02]. There was no change in plasma TGF-beta levels [mean (s.d.)] on either treatment, losartan [before 12.1 (8.9) vs. after 11.9 (9.6) ng/ml, p = 0.68] and quinapril [11.1 (7.9) vs. 11.1 (7.8) ng/ml, p = 0.87). CONCLUSION: In Asian subjects with T2DM and albuminuria, 4 weeks of losartan therapy at 50 mg daily appeared to have greater antialbuminuric effect than 20 mg of quinapril.     

Transplantation of unrelated donor umbilical cord blood utilizing double-unit grafts for five teenagers with transfusion-dependent thalassemia

To augment graft cell dose, we evaluated the safety of the combined transplantation of two partially HLA-matched umbilical cord blood (UCB) units. Five patients with transfusion-dependent thalassemia, median age 11.1 years (range 10-13.1), received 2 UCB units after myeloablative conditioning. Cord blood units were a 4/6-HLA-match or better with the recipient, and contained a minimum combined pre-freeze CD34 cell dose of 3.0 x 10(5)/kg. All patients engrafted at a median of 15 days (range 12-19). Four patients with durable trilineage engraftment showed acute grade I-III GVHD; none developed extensive chronic GVHD until the date of last contact. The median times to red blood cell transfusion independence and platelet engraftment were 32 and 49 days after transplant, respectively. With a median follow-up of 18.5 months (range 11-32), four patients transplanted with UCB from two different partially HLA-matched donors were transfusion-independent. Therefore, transfusion of two partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in long-term recipients of multiple transfusions for thalassemia.     

Atypical manifestation of Vibrio vulnificus septicaemia

Vibrio vulnificus is a Gram‐negative marine bacterium that may cause local wound infection, gastroenteritis, or septicaemia. Fatal septicaemia usually presents with fever, shock, and large haemorrhagic bullae on the legs. This report is about a man who had severe V. vulnificus septicaemia but presented with atypical features of leg pain and diffuse purpuric skin lesions. V. vulnificus septicaemia should be suspected if the following are present: septic shock, leg pains associated with diffuse purpuric skin lesions, recent consumption of raw seafood, and a past medical history of liver cirrhosis.     

A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancers. HPV E6 and E7 are two viral oncoproteins that are consistently expressed in HPV infections and HPV-associated malignancies. We have previously developed DNA vaccines encoding calreticulin (CRT) linked either to HPV type 16 (HPV-16) E6 or to HPV-16 E7, both of which generated significant antitumor effects against E6- and E7-expressing tumors. In this study, we demonstrate that simultaneous vaccination of C57BL/6 mice or HLA-A2 transgenic mice with both CRT/E6 and CRT/E7 DNA vaccines generates significant E6- and E7-specific T-cell immune responses in vaccinated mice. Furthermore, combined vaccination with both CRT/E6 and CRT/E7 DNA generates significantly better therapeutic antitumor effects against HPV E6- and E7-expressing tumors than vaccination with either CRT/E6 DNA or CRT/E7 DNA alone. Our data suggest that it may be desirable to combine DNA vaccines targeting E6 with DNA vaccines targeting E7 to develop effective immunotherapeutic strategies for control of HPV infection and HPV-associated lesions in a clinical setting.     

A population-based study investigating the association between metabolic syndrome and hepatitis B/C infection (Keelung Community-based Integrated Screening study No. 10)

OBJECTIVES: We aimed to assess the association between metabolic syndrome (MS) and hepatitis B/C virus infection using a large population-based study. DESIGN AND METHODS: A population-based cross-sectional study design was adopted with a total of 53,528 subjects being enrolled from the integrated multiple diseases screening program in Keelung, Taiwan. Evidence of past hepatitis B/C infection, acquired during childhood or as a young adult, was identified during the two-stage liver cancer screening part of the process. Information on biochemical markers and anthropometric measures related to MS, such as fasting blood sugar, triglyceride and high-density lipoprotein (HDL), abdominal circumference and blood pressure (BP), were collected routinely while screening for hypertension, type 2 diabetes, and hyperlipidemia. Logistic regression was used to estimate odds ratios and related 95% confidence intervals for the associations between MS and hepatitis B/C infection. RESULTS: High blood pressure (SBP > or = 135 mmHg or DBP > or = 85 mmHg) (adjusted odd ratio: 0.89 (0.83-0.94)) and high triglyceride (> or = 150 mg/dl) (adjusted odds ratio: 0.65 (0.60-0.69)) were, after adjusting for gender and age, inversely associated with being HBsAg positive (P<0.05). The likelihood of developing MS was lower in the HBsAg positive than the HBsAg negative (adjusted odds ratio: 0.84 (0.76-0.93)). A positive association between being anti-HCV positive and having low serum HDL (male <40 mg/dl, female <50 mg/dl) was also noted (adjusted odds ratio: 1.61 (1.37-1.88) after controlling for gender and age). High triglyceride was inversely associated with being anti-HCV positive (adjusted odds ratio: 0.63 (0.55-0.71). CONCLUSIONS: There is an inverse association between MS and hepatitis B virus infection whereas the association was heterogeneous for HCV infection with a positive association with abnormal serum HDL but an inverse association with hypertriglyceridemia.     

Loss of cyclin D1 and p16 expression correlates with local recurrence in nasopharyngeal carcinoma following radiotherapy.

BACKGROUND: The cyclin D1/p16/Rb pathway plays a critical role in tumorigenesis and each component of this pathway may be affected in various malignancies. The purpose of this study was to investigate the expression and prognostic significance of these proteins in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Sixty-five patients undergoing radiotherapy for NPC were analyzed. The expression of cyclin D1, p16 and pRb was evaluated with immunohistochemical analysis of archived pretreatment tumor materials and expression of these proteins was correlated with clinicopathological parameters. RESULTS: Positive expression of cyclin D1 was observed in 43 of 65 NPCs (66%). p16 and pRb inactivation was identified in 42 of 65 (65%) and four of 65 (6%) tumors, respectively. All but seven tumors (58 of 65, 89%) contained at least one alternation in the cyclin D1/p16/Rb pathway. Loss of cyclin D1 as well as p16 was closely related to local recurrence after radiotherapy for NPC (P = 0.015 and 0.047). No association between pRb expression and clinicopathological outcome was apparent. CONCLUSIONS: The study's results suggest that the cyclin D1/p16/Rb pathway plays an important role in NPC tumorigenesis. We also find that cyclin D1 and p16 protein levels in NPC may be of use clinically as a predictor of local tumor control.