Influence of age,risk factors,and cardiovascular and renal disease on arterial stiffness: clinical applications

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality.

Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age.

Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.     

Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis

BACKGROUND & AIMS: We tested whether the attenuation of experimental colitis by live probiotic bacteria is due to their immunostimulatory DNA, whether toll-like receptor (TLR) signaling is required, and whether nonviable probiotics are effective. METHODS: Methylated and unmethylated genomic DNA isolated from probiotics (VSL-3), DNAse-treated probiotics and Escherichia coli (DH5 alpha) genomic DNA were administered intragastrically (i.g.) or subcutaneously (s.c.) to mice prior to the induction of colitis. Viable or gamma-irradiated probiotics were administered i.g. to wild-type mice and mice deficient in different TLR or in the adaptor protein MyD88, 10 days prior to administration of dextran sodium sulfate (DSS) to their drinking water and for 7 days thereafter. RESULTS: Intragastric and s.c. administration of probiotic and E. coli DNA ameliorated the severity of DSS-induced colitis, whereas methylated probiotic DNA, calf thymus DNA, and DNase-treated probiotics had no effect. The colitis severity was attenuated to the same extent by i.g. delivery of nonviable gamma-irradiated or viable probiotics. Mice deficient in MyD88 did not respond to gamma-irradiated probiotics. The severity of DSS-induced colitis in TLR2 and TLR4 deficient mice was significantly decreased by i.g. administration of gamma-irradiated probiotics, whereas, in TLR9-deficient mice, gamma-irradiated probiotics had no effect. CONCLUSIONS: The protective effects of probiotics are mediated by their own DNA rather than by their metabolites or ability to colonize the colon. TLR9 signaling is essential in mediating the anti-inflammatory effect of probiotics, and live microorganisms are not required to attenuate experimental colitis because nonviable probiotics are equally effective.     

Management of acute osteoporotic vertebral fractures: a nonrandomized trial comparing percutaneous vertebroplasty with conservative therapy

PURPOSE: We sought to determine whether percutaneous vertebroplasty--which involves the injection of cement to stabilize a fractured vertebral body--may be an effective treatment for vertebral fracture. METHODS: We enrolled 79 consecutive osteoporotic patients (24 men and 55 women; ages 51 to 93 years) presenting with acute vertebral fractures. Clinical characteristics and bone densitometry were measured at baseline. Pain scores (on a 0 to 25 scale) and levels of function (on a 0 to 20 scale) were recorded on presentation, at 24 hours, at 6 weeks, and 6 to 12 months after therapy. RESULTS: Fifty-five patients (70%) were treated by percutaneous vertebroplasty and 24 (30%) were treated by conservative therapy alone. They were followed for a mean of 215 days (range, 57 to 399 days). The baseline clinical characteristics, bone densitometry, and fracture data were similar in the two groups. Twenty-four hours after vertebroplasty, there was a 53% reduction in pain scores (from 19 to 9; P = 0.0001) and a 29% improvement in physical functioning (from 14 to 18; P = 0.0001), whereas pain scores and physical functioning remained unchanged at 24 hours in the patients treated conservatively (both P = 0.0001 compared with the changes after percutaneous vertebroplasty). Thirteen patients (24%) treated by percutaneous vertebroplasty were able to cease all analgesia after 24 hours (P = 0.0001 compared with none of the 24 patients treated conservatively). Clinical outcomes at 6 weeks and 6 to 12 months were similar in both groups. CONCLUSION: When compared with conservative therapy, percutaneous vertebroplasty results in prompt pain relief and rapid rehabilitation. In experienced hands, it is a safe and effective procedure for treating acute osteoporotic vertebral compression fractures.     

Therapeutic value of pretherapeutic extraperitoneal laparoscopic staging of locally advanced cervical carcinoma

BACKGROUND: Although cervical cancer is clinically staged, surgery has long been considered the best means to assess extrapelvic disease and remains the gold standard for the detection of both intraperitoneal spread and small volume nodal metastases. The objective of this study was to determine short- and long-term outcomes for patients with locally advanced cervical cancer who underwent pretherapeutic laparoscopic staging. METHODS: From 1997 to 2004, 184 patients with stages IB2-IVA cervical cancer underwent pretherapeutic laparoscopic staging procedure including transperitoneal abdomino-pelvic exploration and extraperitoneal bilateral infrarenal paraaortic lymph node dissection. Patients were then treated with definitive radiotherapy tailored according to the staging results. RESULTS: The median age and BMI were respectively 45.8 years old and 27.1 kg/m2. Most lesions were squamous (n=172) and clinical stage was evenly distributed. Median operative time was 155 min with an average of 20.8 lymph nodes removed. Postoperative hospital stay averaged 1.4 days. Major complications included 1 intraoperative ureteral injury and 1 postoperative bowel obstruction from an umbilical trocar site hernia. The final pathology revealed that 44 patients (24.3%) had metastatic disease within paraaortic lymph nodes. With a median follow-up of 26.8 months (average 32.9), 67 patients (36.4%) had recurrent disease. Overall 5-year survival rate was 58.3%. Successful resection of positive lymph node correlated with a survival advantage. CONCLUSIONS: Pretherapeutic laparoscopic assessment of patients with locally advanced cervical cancer offers valuable information for individualized treatment planning with minimal morbidity. This appears to be a therapeutic effect with resection of positive nodes followed by a tailored chemoradiation therapy.     

The impact of video-assisted thoracic surgery (VATS) in patients with suspected advanced ovarian malignancies and pleural effusions

OBJECTIVES: We previously reported our initial experience of patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent video-assessed thoracic surgery (VATS) before planned abdominal exploration. The objective of this study was to report the surgical findings and management of patients who underwent VATS in an update of our experience. METHODS: We performed a retrospective review of all patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent VATS for assessment of extent of intrathoracic disease at our institution between 6/01 and 8/05. RESULTS: Twenty-three patients with a median age of 61 years (range, 36-79) were identified. VATS was performed for right-sided effusions in 17 patients (74%), and a median of 1350 ml (400-3700 ml) of pleural fluid was drained. VATS demonstrated macroscopic disease in 15 (65%) patients, with nodules >1 cm in 11/15 (73%), and nodules <1 cm in 4/15 (27%). Macroscopic intrathoracic disease was found in 4/10 (40%) patients with negative cytology. Intrathoracic cytoreduction was performed in 3/11 patients (27%) with intrathoracic disease >1 cm. After VATS, 12/23 patients (52%) underwent primary surgical management, with cytoreduction to < or =1 cm achieved in 11/12 patients (92%). The other eleven patients received primary chemotherapy after undergoing diagnostic laparoscopy alone (4/11) or no further abdominal exploration (7/11). Nine of these patients proceeded to interval cytoreduction, while 2 had pathology demonstrating upper gastrointestinal and lymphoma primaries at the time of VATS. Final diagnosis of primary site of disease included: ovary, 14 (61%); endometrial, 2 (9%); dual ovarian/endometrial primaries, 1 (4%); fallopian tube, 1 (4%); primary peritoneal, 1 (4%); other, 4 (17%). Overall, findings at VATS altered primary surgical management in 11/23 (48%) patients. CONCLUSIONS: Sixty-five percent of patients with suspected advanced ovarian cancer and moderate to large pleural effusions had gross intrathoracic disease identified at VATS, with the majority (11/15, 73%) having disease >1 cm in diameter. Use of VATS allows for assessment of intrathoracic disease and may help identify candidates for primary cytoreductive surgery and possible intrathoracic cytoreduction versus neoadjuvant chemotherapy.     

Birth weight and size: charts and equations

Objectives

To construct new reference charts and equations for birth weight and birth size using a large and exhaustive sample of newborns. To compare this new references with previous ones.

Materials and methods

The study data were obtained from a single health authority (the birth registry of Yvelines, a French Territorial division of 1.4 million people) over 3 years. Multiple pregnancies were excluded. No data were excluded on the basis of abnormal biometry or birth weight. For each measurement, a least square regression model with high order polynomials was fitted to predict mean, standard deviation and therefore Z scores of birth weigh and birth size at any gestational age at birth from 25 to 42 weeks'.

Results

There were 58 934 and 56 956 measurements included for weight and size at birth respectively. New charts and equations for Z scores calculations, adjusted for sex, are reported based on polynomial regression methods.

Conclusion

We present new French reference charts and equations for birth biometrics. Because they were derived from a very large and unselected sample, there might be more relevant to clinical practice than others and can be easily used to compute centiles and Z-scores.     

A standardised ultrasonic diagnosis and an accurate prevalence for the retroverted uterus in general gynaecology patients

Transvaginal ultrasound with an empty bladder is recommended as a standardised ultrasonic technique for the accurate diagnosis of the retroverted uterus. Using this method, the prevalence of the retroverted uterus in 480 general gynaecological patients attending for subspecialist gynaecological ultrasound was 18%. The anteverting effect of the full bladder required for transabdominal ultrasound reduces the prevalence of the retroverted uterus to 13% (P < 0.001).     

Screening for Down syndrome using first-trimester combined screening followed by second trimester ultrasound examination in an unselected population

BACKGROUND: Recent studies have reported the efficacy of first trimester combined screening for Down Syndrome based on maternal age, serum markers (human chorionic gonadotropin, pregnancy-associated plasma protein A), and ultrasound measurement of fetal nuchal translucency. However, those do not incorporate the value of the widely accepted routine 20-22 week anomaly scan. STUDY DESIGN: We carried out a multi-centre, interventional study in the unselected population of a single health authority in order to assess the performance of first trimester combined screening, followed by routine second trimester ultrasound examination and/or screening by maternal serum markers (free beta-hCG and alpha-fetoprotein measurement or total hCG, alpha-fetoprotein and unconjugated estriol measurement) when incidentally performed. Detection and screen positive rates were estimated using a correction method for non verified issues. A cost analysis was also performed. RESULTS: During the study period, 14,934 women were included. Fifty-one cases of Down Syndrome were observed, giving a prevalence of 3.4 per 1000 pregnancies. Of these, 46 were diagnosed through first (N=41) or second (N=5) trimester screening. Among the 5 screen-negative Down syndrome cases, all were diagnosed postnatally after an uneventful pregnancy. Detection and screen positive rates of first trimester combined screening were 79.6% and 2.7%, respectively. These features reached 89.7 and 4.2%, respectively when combined with second trimester ultrasound screening. The average cost of the full screening procedure was 108 euro (120 $) per woman and the cost per diagnosed Down syndrome pregnancy was 7,118 euro (7,909 $). CONCLUSION: Our findings suggest that one pragmatic interventional two-step approach using first-trimester combined screening followed by second trimester detailed ultrasound examination is a suitable and acceptable option for Down syndrome screening in pregnancy.