Surgical epicardial left ventricular lead versus coronary sinus lead placement in biventricular pacing.

OBJECTIVE: Biventricular pacing has demonstrated improvement in cardiac function in treating congestive heart failure (CHF). Two different operative strategies (coronary sinus vs. epicardial stimulation) for left ventricular (LV) pacing were compared. METHODS: Since April 1999, a total of 86 patients (pts, age: 63+/-10 years) with depressed systolic LV function (mean ejection fraction 24+/-9%), left bundle-branch-block (mean QRS 182+/-22 ms) and congestive heart failure NYHA III or higher were enrolled. For biventricular stimulation coronary sinus (CS) leads were placed in 79 pts. Nine of these devices were converted to surgical epicardial LV-leads, because of CS-lead failure. In 7 patients epicardial LV-leads were initially implanted surgically, accounting for a total of 16 pts with surgical placed epicardial steroid-eluting LV-leads. For these, a limited left-lateral thoracotomy (7+/-4 cm) was used. Thirty-three (38%) pts had an indication for a defibrillator. The mean follow-up time was 16.4+/-15.4 months (0.1-45 months), representing 107.1 patient-years. RESULTS: In the biventricular pacing mode, QRS duration decreased to 143+/-16 ms (P<0.001). Threshold capture of the CS-leads increased significantly compared to surgically placed epicardial leads (18 month control: 2.2+/-1.4V/0.5 ms vs. 0.7+/-0.3V/0.5 ms), which had no increase in threshold (P<0.001). At the 18 month follow-up 7 CS-leads had a threshold of >4V/0.5 ms vs. epicardial leads which were under 1.1V/0.5 ms, except for one (1.8V/0.5 ms). After CS-lead implantation 25 LV-lead related complications occurred, (failed implantation, CS-dissection, loss of pacing capture, diaphragm stimulation or lead dislodgment), vs. one dislodgement after surgical epicardial lead placement (P<0.05). Correct lead positioning (obtuse marginal branch area) was achieved in all surgical epicardial placements but only in 70% with CS-leads (P<0.03). In the follow up period, 9 pts died (4 cardiac related). Heart transplantation was necessary in 4 pts due to deterioration of the cardiomyopathy. CONCLUSIONS: Surgical epicardial lead placement revealed excellent long-term results and a lower LV-related complication rate compared to CS-leads. Although, the approach via limited thoracotomy for biventricular pacing is associated with 'more surgery', it is a safe and reliable technique and should be considered as an equal alternative.     

Can marital selection explain the differences in health between married and divorced people? From a longitudinal study of a British birth cohort

In view of the rising divorce rates, the impact of divorce on health has an increasing importance in public health. The differentials in health between the married and the divorced may be explained by ‘marital selection’ and ‘marital protection’. Using longitudinal data from a study of the 1958 British birth cohort, factors that select people into divorce were identified from the areas of socio-economic status, health, and attractiveness, which included physical attractiveness, health-related behaviour and temperament. Evidence for both positive and adverse selection is found. The different sets of selection factors for females and males appear to be in line with gender role expectations. The health differentials between married and divorced men were weak and can be explained away by the selection factors. Having controlled for the selection effects, there were still significant associations between divorce and physical and psychological health in women. Though these unexplained differentials cannot be definitely interpreted as the consequences of marital dissolution, this interpretation remains plausible.     

Adjustment of metabolism,catecholamines and β-adrenoceptors to 90 min of cycle ergometry

Adrenaline infusion of 0.1 g · kg^–1 · min^–1 in healthy volunteers results in an increase of hepatic glucose production, an increase of the absolute number of occupied -adrenoceptors and specific changes in metabolism. To compare these effects with the changes induced by an endogenous catecholamine release, we investigated healthy volunteers during cycle ergometry. After fasting at least 14 h seven healthy subjects exercised for 90 min at an intensity of 20% below their individual anaerobic threshold. The rate of glucose production as well as the turnover rates of alanine and leucine were calculated using stable isotope tracers. High and low affinity -adrenergic binding sites on lymphocytes were determined by an equilibrium binding assay with (–)¹²⁵ Iodocyanopindolol. After 90 min of cycling the rate of appearance of glucose increased significantly from means of 2.0 (SD 0.2) to 2.65 (SD 0.50) mg · kg^–1 · min^–1 with unchanged blood concentrations of glucose and lactate. The flux of the amino acids alanine and leucine decreased significantly from means of 0.91 (SD 0.21) to 0.62 (SD 0.14) mg · kg^–1 · min^–1 and from 0.40 (SD 0.05) to 0.32(SD 0.04) mg · kg^–1 · min^–1, respectively. The mean free fatty acid concentration increased significantly from 0.65 (SD 0.33) to 1.27 (SD 0.45) mmol · l^–1 during the endurance trial. The increase of glucose turnover and the decrease of amino acid flux point to a metabolic shift towards enhanced utilization of free fatty acids. Adrenaline and noradrenaline concentrations showed a moderate but significant increase from means of 0.61 (SD 0.20) to 0.99 (SD 0.36) nmol · l^–1 and from 2.27 (SD 0.75) to 3.46 (SD 0.38) nmol · 1^–1, respectively. The number of high affinity -adrenergic binding sites per cell (-adrenoceptors) nearly doubled from 770 (SD 130) to 1490 (SD 150) during 90 min of cycling. The observed endogenous plasma catecholamine concentrations were not sufficient to change significantly the relative receptor occupancy. This would seem to indicate that the aerobic exercise induced effects depended more on the absolute number of occupied -adrenoceptors than on their relative receptor occupancy. When compared to the results of the adrenaline infusion experiment the increases of the hepatic glucose production and the increase of -adrenoceptors were very similar in both groups despite ten times higher adrenaline plasma concentrations in the infusion group. This would seem to indicate that -adrenoceptors mediated effects do not correlate with catecholamine plasma concentrations.     

The MDR1 polymorphisms at exons 21 and 26 predict steroid weaning in pediatric heart transplant patients

Various polymorphisms of the MDR1 gene that encodes for P-glycoprotein (P-gp), a transmembrane pump, have been identified. A silent mutation C3435T in exon 26 and a G2677T mutation in exon 21 have been correlated with P-gp expression and function in humans. The objectives of this study were (a) to determine whether the MDR1 exon 21 and exon 26 polymorphisms were related to steroid weaning in a pediatric heart transplant (HTx) population, and (b) to determine whether an association exist between the MDR1 exon 21 and exon 26 polymorphisms in these patients. Sixty-nine pediatric HTx patients were studied. MDR1 genotyping was determined by polymerase chain reaction amplification, sequencing the DNA, and sequence evaluation using Polyphred software (University of Washington) to identify genotypes. The steroid dose at 1 year post-transplantation was recorded. For steroid weaning at one year post-HTx for MDR1 C3435T, 12 of 18 (67%) patients in the CC genotype were still on prednisone, whereas only 18 of 47 (38%) of the CT/TT group were still receiving prednisone (p = 0.04). Similar results were observed for the MDR1 G2677T genotyping and steroid weaning. Forty-three of 46 patients (93.5%) who have MDR1 C3435T allele also have a mutant G2677T allele (p < 0.001). We conclude that (a) a significantly larger number of MDR1 3435 CC HTx patients remain on steroids at 1 year after transplantation, and (b) the MDR1 C3435T genotype is associated with the G2677 genotype in pediatric HTx patients.     

Spontaneous perforation of the rectosigmoid colon: a report of 2 cases

Spontaneous perforation of rectosigmoid colon is rare but usually results in severe peritonitis, with very high mortality. Two cases of spontaneous rectosigmoid perforations are reported here along with a brief literatures review.     

In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L. , namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl（1→ 2）-[-β-D-xylopyranosyl（ 1 → 3 ） 3-β- D-glucopyranosyl （ 1 → 4 ）- 1- α-L-rhamnopyranosyl （ 1 → 2 ） 3-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranpyranosyl（1→2）-[-β-D-xylopyranosyl（1→ 3）3-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida para psilosis , Candida tropicalis , Candida krusei , and Cryptococcus neo f ormans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans （MIC80 = 4.4, 9.4 mg/ml）, C. neoformans （MIC80 =10.7, 18.7 mg/ml） and inherently resistant C. krusei （MIC80 =8.8, 18.4 mg/ml）. So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.     

Adoptive immunotherapy of metastatic breast cancer: present and future

Breast cancer is a systemic disease with a primarily local component. Besides surgical resection and irradiation of the locoregional tumor setting, central therapeutic aim is the elimination of disseminated micrometastatic tumor cells using cytostatic and/or hormonal treatment. Nevertheless, in the course of time a majority of patients suffer from systemic recurrence in the form of distant metastases. Intriguingly, in this connection, intratumoral cytotoxic T lymphocytes might serve as independent predictors of treatment efficacy and clinical outcome. Loss of immune balance (tumor dormancy) during intensive cross talk between T cells and tumor cells in the bone marrow microenvironment is suggested one reason for distant metastatic relapse. In this clinical context, further supportive therapies become increasingly attractive, taking immunological features of breast cancer cells into special account. The present review aims to dissect bone marrow-derived cellular antitumor immune responses and translational immunologic treatment options regarding their actual relevance to patients’ clinical benefit and their future directions in breast cancer management.