Influence of E. coli Strain Nissle 1917 (EcN) on Intestinal Gas Dynamics and Abdominal Sensation

E. coli strain Nissle 1917 (EcN) is a probiotic clinically used with various indications. However, especially at the beginning of treatment, some patients report abdominal bloating. In a prospective, randomized, double-blind study in 30 healthy individuals we assessed the influences of EcN on intestinal gas dynamics and abdominal sensation. After one week without medication volunteers orally received 2.5–25 × 10⁹ colony-forming units of EcN or placebo per day for 21 days. EcN was well tolerated and did not significantly affect abdominal symptoms, stool frequency or stool consistency. During gas challenge at different days no difference in the perception scores (range from 0 = no perception to 6 = pain) was observed between the two groups: the mean perception score was 1.2 (SD 0.2) in the EcN group and 1.4 (SD 0.2) in the placebo group. EcN had no relevant influence on intestinal gas dynamics.     

Estimation of left ventricular myocardial function by the ejection fraction in isolated, chronic, pure aortic regurgitation

In patients with aortic regurgitation (AR), the left ventricular (LV) ejection fraction (EF) may not adequately reflect depressions of myocardial contractility due to decreased aortic impedance. The sensitivity of end-systolic pressure-volume relations and stress-volume relations in detecting myocardial depression in patients with AR was studied. In 12 patients with normal valvular function but with varying LV function (due to coronary heart disease in 9 patients and dilated cardiomyopathy in 3 patients) (group 1), and in 8 patients with AR (group 2), LV angiography was performed before and after sublingual application of isosorbide dinitrate. Heart rate was kept constant by right atrial pacing. In group 1, the slope k of the end-systolic pressure-volume relation was to EF at rest: k = 0.091.e0.051 EF; r = 0.88. In AR, this relation was shifted significantly to the right: k = 0.019.e0.066 EF; r = 0.92. This shift persisted when the end-systolic stress-volume relation instead of the end-systolic pressure-volume relation was calculated. Thus, in patients with AR the end-systolic pressure-volume relation is flatter than that in patients with intact valvular function at a given EF. The same is true for the end-systolic stress-volume relation. The data indicate that EF overestimates myocardial contractility in AR compared with end-systolic pressure-volume or stress-volume relations. This overestimation is probably a result of decreased aortic impedance in AR.     

Discontinuation of nonsteroidal anti-inflammatory drug therapy and risk of acute myocardial infarction

BACKGROUND: Systemic inflammation has been shown to be associated with an increased risk of acute myocardial infarction (AMI). However, the effect of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on the risk of AMI has not yet been well defined. We therefore studied the risk of AMI during NSAID exposure and after the cessation of NSAID therapy. METHODS: We conducted a large case-control analysis on the British General Practice Research Database. The study included 8688 cases with a first-time AMI between 1995 and 2001 and 33 923 controls, matched to cases on age, sex, calendar time, and general practice attended. RESULTS: After adjusting for hypertension, hyperlipidemia, diabetes mellitus, ischemic heart disease, rheumatoid arthritis, systemic lupus erythematosus, acute chest infection, body mass index, smoking, and aspirin use, the risk of AMI was 1.52 (95% confidence interval [CI], 1.33-1.74) for subjects who stopped taking NSAIDs 1 to 29 days prior to the index date, compared with nonusers. The risk was highest in subjects with rheumatoid arthritis or systemic lupus erythematosus (adjusted OR, 3.68 [95% CI, 2.36-5.74]) and for subjects who discontinued therapy with NSAIDs after previous long-term use (adjusted OR, 2.60 [95% CI, 1.84-3.68]). Current and past NSAID use (discontinued therapy >/=60 days prior to the index date) were not associated with an increased risk of AMI (adjusted OR, 1.07 [95% CI, 0.96-1.19] and 1.05 [95% CI, 0.99-1.12], respectively). CONCLUSION: Our findings suggest that the risk of AMI is increased during several weeks after the cessation of NSAID therapy.     

Mitral valve closure and left ventricular filling time in patients with VDD pacemakers. Assessment of the onset of left ventricular systole and the end of diastole

The effect of mitral valve closure on left ventricular filling time and its relation to the onset of systole were assessed from mitral valve echocardiograms and simultaneous apex cardiograms in 21 normal subjects, 11 patients with left bundle branch block, and 19 patients with VDD pacemakers programmed for atrioventricular intervals of 50, 150, and 250 ms. The interval between the electrocardiograph Q wave and the apex cardiogram upstroke was similar in normal subjects and patients with left bundle branch block, but was significantly longer in patients with VDD pacemakers at all atrioventricular intervals. Similarly there was little difference in the time interval between the Q wave and mitral valve closure in normal individuals and patients with left bundle branch block but this was considerably delayed in VDD pacemaker patients with the atrioventricular interval set at 50 ms. With increasing atrioventricular intervals the mitral valve closed significantly earlier, whereas the onset of left ventricular systole and the timing of mitral valve opening remained unchanged. Thus as a result of earlier mitral valve closure left ventricular filling time decreased progressively as the atrioventricular interval was increased. Since the onset of left ventricular systole, with respect to left ventricular stimulation, is considerably delayed in VDD pacemaker patients a short atrioventricular interval is required in these patients to maintain the normal time relations between atrial and ventricular contraction and hence maximise left ventricular filling.     

Robotic-assisted total mesorectal excision (TME) for rectal cancer results in a significantly higher quality of TME specimen compared to the laparoscopic approach—report of a single-center experience

Aim

Robotic surgery allows for a better visualization and more precise dissection especially in the narrow male pelvis and mid and lower third of the rectum. However, superiority to laparoscopic TME has yet to be proven. We therefore analyzed short-term outcomes of laparoscopic and robotic low anterior rectal resection for rectal cancer.

Patients and methods

From 2011 to 2016, 44 robotic (RTME) and 41 laparoscopic (LTME) low anterior rectal resection with total mesorectal excision were performed at a single institution. Specimen quality was assessed and reported by an independent pathologist following international guidelines.

Results

The groups did not differ significantly regarding gender, age, ASA stage, BMI, and distance of the lower tumor margin from the anal verge. More patients in the RTME group underwent preoperative chemoradiation (43.2 vs. 19.5%, p?=?0.019). The quality of the TME specimen was significantly better in the RTME group (complete/nearly complete/incomplete for RTME 97/0/3% and for LTME 78/17/5%, p?=?0.03). The conversion rate tended to be lower in the RTME group (7 vs. 17%, p?=?0.143). There was no difference in CRM positivity between the groups.

Conclusion

Robotic surgery is safe and can improve the quality of TME for rectal cancer compared to laparoscopy. Any effect on long-term survival remains to be established.

     

Alfalfa seeds lower low density lipoprotein cholesterol and apolipoprotein B concentrations in patients with type II hyperlipoproteinemia

Fifteen patients with hyperlipoproteinemia (HLP), types IIA (n = 8), IIB (n = 3) and IV (n = 4) were given 40 g of heat prepared alfalfa seeds 3 times daily at mealtimes for 8 weeks with otherwise unchanged diet. In patients with type II HLP alfalfa treatment caused after 8 weeks a maximal lowering of pretreatment median values of total plasma cholesterol from 9.58 to 8.00 mmol/l (P less than 0.001) and low density lipoprotein (LDL) cholesterol from 7.69 to 6.33 mmol/l (P less than 0.01), which corresponds to decreases of 17% and 18%, respectively. Maximal decrease was 26% in total cholesterol and 30% in LDL cholesterol. In two patients with hypercholesterolemia the LDL cholesterol decreased less than 5%. Apolipoprotein B decreased in the same period from 2.17 to 1.43 g/l (P less than 0.05) in type II HLP, corresponding to 34% decrease, whereas apolipoprotein A-I did not change. Body weight increased slightly during the first 4 weeks of alfalfa treatment (P less than 0.001) probably because of the caloric content in the alfalfa seeds. After cessation of treatment, all lipoprotein concentrations returned to pretreatment levels. We conclude that alfalfa seeds can be added to the diet to help normalize serum cholesterol concentrations in patients with type II HLP.     

Fluorescence-activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes.

Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion genes tested were passed into the germ line, indicating that FACS does not significantly affect stem cell totipotency. The pattern of lacZ expression observed in vivo was consistent with that seen in vitro. Both fusion genes were expressed in preimplantation blastulas. However, a fusion gene whose expression was unaffected by in vitro differentiation was ubiquitously expressed in day-10 embryos, while the other, which showed regulated expression in vitro, was restricted to cells located along the posterior neural fold, the optic chiasm, and within the fourth ventricle. These results demonstrate the utility of using promoter trap vectors in conjunction with fluorescence sorting to disrupt developmentally regulated genes in mice.     

3,4-Bis(3′-hydroxyphenyl)hexane — A new mammary tumor-inhibiting compound

Summary The syntheses of the hexestrol derivatives 3,4-bis-(3-hydroxyphenyl)hexane (4a), 3,4-bis(4-fluoro-3-hydroxyphenyl)hexane (4b), 3,4-bis(3, 4dihydroxyphenyl)hexane (4c), and 3,4-bis(3,4-diacetoxyphenyl)hexane (4d) are described. All compounds showed a marked, competitive inhibition of the estradiol receptor interaction (K _a4c>K_a4a>K_a4d>K_a4b). Evaluated in the mouse uterine weight test compounds 4c and 4d almost reached the estrone effect, whereas 4a and 4b did not produce full uterotrophic response. Compounds 4a-d antagonized the estrone stimulated uterine growth of the immature mouse. Compound 4a (NSC-297170) exhibited a specific, dose-related growth inhibition of the estrogen responsive MCF-7 human breast tumor cell line. Tested on the 9,10-dimethyl-1,2-benzanthracene-induced hormonedependent mammary adenocarcinoma of the Sprague-Dawley rat all compounds showed marked inhibition of tumor growth. As in all experiments compounds 4a and 4b, which is resistant to hydroxylation in 4position exhibited an identical pattern of action, which is different from that shown by compound 4c, the effect of compound 4a cannot be explained by its possible catechol metabolite 4c.Supported by grants from the Deutsche Forschungsgemeinschaft and the Verband der Chemischen Industrie-Fonds der Chemischen Industrie     

Fabry disease: focus on cardiac manifestations and molecular mechanisms

PATHOGENESIS: Fabry disease is an inherited lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. The enzyme deficiency results in accumulation of glycosphingolipids in the lysosomes n nearly all cell types and tissues leading to a multisystem disease. MANIFESTATIONS include painful crisis, angiokeratomas, corneal dystrophy, and hypohydrosis. The severe renal, cerebrovascular, and cardiac involvement is predominantly responsible for premature mortality in Fabry patients. The disease is X-linked and manifests primarily in hemizygous males but also heterozygous females can be affected. CARDIAC INVOLVEMENT is frequent in Fabry disease. Patients develop hypertrophic cardiomyopathy, arrhythmias, conduction abnormalities, and valvular abnormalities. Although Fabry disease leads to a complex clinical syndrome, there are studies indicating that manifestations can be limited to the heart. The isolated cardiac variant of Fabry disease seems to be more common than previously thought: around 3-6% of male patients with left ventricular hypertrophy seem to suffer from this disease variant. ENZYME REPLACEMENT THERAPY: Recent advances in molecular biology and genetic engineering have enabled the development of enzyme replacement therapy in Fabry disease. Results from two independent therapy studies are indeed promising: Infusion of the enzyme preparation seems to be well tolerated and effective in catabolizing the lipid deposits. This enzyme replacement therapy could be one of the first examples for causal treatment of left ventricular hypertrophy. Therefore, early diagnosis of hypertrophy patients with the cardiac variant of Fabry disease is important.     

Ultrasound navigation through the heart for off-pump aortic valved stent implantation: new tools for new goals.

PURPOSE: To validate the use of simultaneous intracardiac and intravascular ultrasound (IVUS) guidance for periprocedural dimension assessment, Residual-Coronary/Sinus-Stent Index (RCSSI) estimation, target site identification, deployment monitoring, and quality control of off-pump aortic Valved Stent implantation. METHODS: Five pigs (56+/-5 kg) underwent off-pump orthotopic aortic valve implantation using a custom-made self-expanding Valved Stent. Intracardiac ultrasound (AcuNav) was introduced via the right femoral vein. After left-sided thoracotomy, pursestring sutures were placed on the left ventricular apex. Following heparinization, a guidewire was inserted through the apex and advanced over the aortic valve under fluoroscopy. A wire-guided IVUS catheter transducer (6-F, 12.5-MHz) was inserted and the aortic target site identified. IVUS probe location was tracked with AcuNav, and measures of the aortic root were taken by both. After removal of the IVUS, the Valved Stent delivery system was introduced over the guidewire under fluoroscopy and AcuNav monitoring; the Valved Stent was deployed over the native valves. In vivo assessment included leaflet motion, planimetric valve orifice and RCSSI (stent to aortic wall distance/coronary diameter) calculations, coronary blood flow characteristics, transvalvular gradient, regurgitation, and paravalvular leaking in combination with continuous cardiac output measures. Macroscopic analysis was performed at necropsy. RESULTS: IVUS dimensions of the aortic root were equal to AcuNav and necropsy dimensions. Both tools showed good valvular function, with full valvular opening and closing in 3 of 5 valves. At necropsy, the 3 aortic Valved Stents were safely anchored. One Valved Stent was placed supra-annularly; 2 dislodged into the left ventricle because of size mismatch. One Valved Stent showed a moderate to severe paravalvular leak. CONCLUSIONS: Simultaneous intracardiac and intravascular ultrasound-guided off-pump orthotopic aortic Valved Stent implantation via left sided thoracotomy is feasible in an animal model. IVUS and intracardiac ultrasound allow adequate aortic dimension assessment and Valved Stent delivery monitoring, as well as postimplantation coronary flow evaluation.