Entourage effect for phenolic compounds on production and metabolism of mammary epithelial cells.

Primary culture of mammary epithelial cells (MEC) was exposed to ethyl-acetate, chloroform and hexane extracts of Pistacia lentiscus (lentisk). The hexane extract contained mainly ethyl gallate whereas the chloroform extract contained mainly ethyl-gallate with smaller amount of gallic acid, and the ethyl-acetate extract contained mainly rutin, gallic acid and myricetin. Ethyl acetate extract increased secretion of protein and fat and improved mitochondrial activity. The enhancing effect on protein production was attributed to myricetin, one of the polyphenols in the ethyl-acetate extract whereas gallic acid did not affect protein production or secretion. Interestingly, exposure to the isolated polyphenols did not improve mitochondrial productivity and activity as effectively as exposure to the complete plant extract. The results indicated that polyphenols improve production of milk constituents by MEC, through different modes of action for different polyphenols suggesting an additive or even synergistic effect on production traits of mammary cells.

Pistacia lentiscus extract enhances mammary epithelial cells' productivity by modulating their oxidative status.

We assessed the potential of phenolic compounds from Pistacia lentiscus (lentisk) to enhance production of milk constituents in bovine mammary epithelial cells (MEC). MEC were exposed to 0 (control), 1 or 10 ppm of polyphenols from lentisk ethanolic extract (PLEE) for 24 h. PLEE were absorbed by the MEC plasma membrane, but also penetrated the cell to accumulate in and around the nucleus. PLEE increased triglyceride content in the cell and its secretion to the medium, and significantly increased intracellular lipid droplet diameter. Compared to control, PLEE increased dose-dependently the lactose synthesis, secretion of whey proteins, and contents of casein. To evaluate mitochondrial activity under pro-oxidant load, MEC were preincubated with PLEE and exposed for 2 h to H2O2. Exposure to H2O2 increased the proportion of cells with impaired mitochondrial membrane potential twofold in controls, but not in PLEE-pre-treated cells. Accordingly, proton leakage was markedly decreased by PLEE, and coupling efficiency between the respiratory chain and ATP production was significantly enhanced. Thus, lentisk polyphenols divert energy to production of milk fat, protein and lactose, with less energy directed to cellular damage control; alternatively, PLEE enables MEC to maintain energy and oxidative status under extreme metabolic rate required for milk production and secretion, and reduces the limitation on energy required to support production.

Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNF alpha blockers.

OBJECTIVE: To assess the efficacy and safety of vaccination against influenza virus in patients with rheumatoid arthritis, with special emphasis on the effect of disease modifying antirheumatic drugs (DMARDs), including tumour necrosis factor alpha (TNFalpha) blockers. METHODS: 82 rheumatoid patients and 30 healthy controls were vaccinated with a split-virion inactivated vaccine containing 15 mug haemagglutinin (HA) per dose of each of B/Hong Kong/330/2001 (HK), A/Panama/2007/99 (PAN), and A/New Caledonian/20/99 (NC). Disease activity was assessed by tender and swollen joint count, morning stiffness, evaluation of pain, Health Assessment Questionnaire, ESR, and C reactive protein on the day of vaccination and six weeks later. Haemagglutination inhibiting (HI) antibodies were tested by a standard WHO procedure. Response was defined as a fourfold or more rise in HI antibodies six weeks after vaccination, or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated to assess the immunity of the whole group. RESULTS: Six weeks after vaccination, a significant increase in GMT for each antigen was observed in both groups, this being higher in the healthy group for HK (p=0.004). The percentage of responders was lower in rheumatoid patients than healthy controls (significant for HK). The percentage of responders was not affected by prednisone or any DMARD, including methotrexate, infliximab, and etanercept. Indices of disease activity remained unchanged. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in rheumatoid patients, although lower than in healthy controls. The response was not affected by the use of prednisone or DMARDs.

Are singleton assisted reproductive technology pregnancies at risk of prematurity?

PURPOSE: Our purpose was to determine the risk of premature delivery among singleton pregnancies derived from assisted reproduction technology (ART). METHODS: Ninety-five singleton ART pregnancies and 190 matched spontaneous pregnancies were assessed for preterm delivery rates, pregnancy complications, and cesarean section rates in a retrospective study at an academic medical center. RESULTS: Among the ART singleton deliveries group (n = 95), 19 (20%) were preterm, which was statistically significantly higher than the 4% (8 of 190) found in the control group. Among the pregnancies achieved by intracytoplasmic sperm injection (ICSI) in the severe male-factor infertility subgroup (n = 22), only one preterm delivery occurred (4.5%). CONCLUSIONS: Singleton ART pregnancies are at an increased risk of preterm delivery compared to singleton pregnancies after spontaneous conception. The higher rate may be attributed to various infertility cofactors, such as uterine malformations, previous operative procedures that involved cervical dilatation, and a history of pelvic infection. This is supported by the finding that ICSI-derived pregnancies in couples with strict male-factor infertility are not at an increased risk of preterm delivery.

Real-time intraoperative ultrasound guidance: the transrectal approach.

OBJECTIVE: To assess the role of real-time transrectal ultrasound guidance in complicated gynecologic procedures. DESIGN: In 1998-99, real-time guidance with transrectal ultrasound was utilized in our department to assist the gynecologic surgeon in two procedures: completing the evacuation of the uterine cavity after identification of uterine wall perforation during first trimester termination of pregnancy, and drainage of infected vaginal vault hematoma following hysterectomy. RESULTS: The technique was applied for 11 patients, six abortions and five infected hematomas. All the procedures were completed without any further complications and the patients were discharged on the following day. Follow-up was uneventful. CONCLUSIONS: On-line intraoperative transrectal ultrasound can effectively provide real-time assistance to the gynecologic surgeon during complicated pelvic procedures.

Effect of antibiotic therapy in preterm premature rupture of the membranes on neonatal mortality and morbidity.

The objective of this study was to evaluate the effect of prophylactic antibiotic treatment on prenatal and neonatal outcome after preterm premature rupture of the membranes (P-PROM). The study population consisted of 172 pregnant women admitted to the Rabin Medical Center in Israel with P-PROM at 23-34 gestational weeks. The patients were divided into two groups by mode of expectant management-prophylactic ampicillin and erythromycin (study group, n = 121) or observation only (control group, n = 51) and compared for neonatal outcome. There were no significant differences between the groups in age, gravidity, parity, or gestational age at admission. Significantly more women in the study group had an interval of more than 24 hours from onset of P-PROM to delivery (98 women, 81%) than the control group (32 women, 63%) (p = 0.001). The neonatal mortality rate was significantly lower in the study group (6.6%) than the control group (1 7.6%) (p = 0.03). The lower neonatal mortality rate associated with prophylactic antibiotic treatment in P-PROM has important clinical implications for the effectiveness of this type of management.

Outcome of pregnancies derived from assisted reproductive technologies: IVF versus ICSI.

PURPOSE: To compare the course and outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies. METHODS: A retrospective study was conducted in a university-affiliated IVF unit with 200 patients who conceived in 1996-1997, 100 with ICSI and 100 with IVF. Data were retrieved from our prospectively created computerized database. In addition, all patients were interviewed by telephone, and the interviewing physician completed a detailed questionnaire. Findings for the IVF and ICSI pregnancies were compared. The main outcome measures were maternal age, implantation rate, early pregnancy complications, clinical abortion rate, multiple pregnancy delivery rate, gestational age at delivery, mode of delivery, and birth weight. RESULTS: In all, 238 children were born, including 104 singleton infants (45 IVF, 59 ICSI), 49 twin pairs (28 IVF, 21 ICSI), and 12 triplet sets (3 IVF, 9 ICSI). Statistically significant differences between the ICSI and IVF groups were noted for maternal age (31.3 +/- 4.4 vs. 33.4 +/- 4.8, respectively, P < 0.005) and clinical abortion rate (11% vs. 24%, respectively, P < 0.05). CONCLUSIONS: ICSI pregnancies in our series were characterized by a lower clinical abortion rate than IVF pregnancies, probably because of the mean younger age of the ICSI group.

Pregnancy outcome in women with primary renal disease.

BACKGROUND: The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial. OBJECTIVES: To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency. METHODS: Logistic regression models were formulated to predict successful outcome. RESULTS: Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level. CONCLUSIONS: Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide useful guidelines for counseling women with preexisting renal disease about their prospects for a successful pregnancy in terms of immediate and long-term maternal and neonatal outcome.

Carotid stenting in patients older than 65 years with inoperable carotid artery disease: a single-center experience.

Carotid angioplasty and stenting to treat extracranial carotid stenosis is an alternative (as yet not widely accepted) to high-risk surgery, but its safety and efficacy are little known, especially in elderly patients. We reviewed our 3-year experience of treating 100 elderly patients (> 65 years old) considered to be inoperable (76 men, 24 women, mean age 76+/-10 years, mean follow-up 18+/-9.2 months) and present two case histories. Most (85%) were symptomatic (transient ischemic attacks in 60, stroke in 25); 80 had concomitant coronary artery disease (severe in 30 [defined by > 70% stenosis in two or more epicardial coronary arteries or the left main coronary artery]) and 25 had severe left ventricular dysfunction (ejection fraction < or =20%). The procedure was technically successful in all patients; there was one major stroke and no patient died. Postprocedure, 15% had minor complications: reversible neurological deficit (5%), pulmonary edema (3%), prolonged hypotension (3%), vascular access complications (3%), and neck hematoma (1%). Over 90% of patients were discharged home within 24 hr.

Pre-operative ultrasonographic evaluation of nongravid, enlarged uteri--correlation with bimanual examination.

OBJECTIVE: To correlate the size of the nongravid uterus measured by ultrasound and bimanual examination before hysterectomy, with the actual size of the specimens. PATIENTS AND METHODS: Uterine size of 49 consecutive patients, who underwent elective hysterectomy, was assessed by bimanual pelvic examination, preoperative ultrasonographic evaluation and actual postoperative size. RESULTS: All preoperative ultrasonographic uterine dimensions significantly correlated with the corresponding actual dimensions of the uterine specimens. Furthermore, ultrasonographic uterine length had the best correlation with uterine size estimation by bimanual examination. A formula was established in an attempt to calculate clinical uterine size by gestational week, using preoperative ultrasonographic dimensions. CONCLUSIONS: By using the aforementioned formula, ultrasonographic uterine dimensions can be extrapolated to uterine size in terms of gestational week, and therefore, be applicable to traditional clinical practice.

Validation of Doppler FloWire for measurement of coronary flow reserve in humans.

Previous studies have validated the 133Xenon (133Xe) method to assess regional myocardial blood flow and coronary flow reserve (CFR). Doppler FloWire (DFW) has been used recently for measuring CFR to assess the physiological significance of coronary stenosis. Data obtained by DFW has never been correlated to 133Xe. Our study compared data from DFW measurement of CFR to that obtained by 133Xe in 31 consecutive patients with variable coronary stenosis. Regional myocardial blood flow was measured by assessing the rate constants of 133Xe washout using multicrystal gamma camera after injection (20 millicuries) in the right or left coronary artery. CFR was assessed by measuring resting and hyperemic coronary blood flow by 133Xe and DFW using i.v. adenosine (140 mcg/k/min x 3 min). CFR was also measured by DFW giving intracoronary (i.c.) adenosine (12 microg in the right coronary, 18 microg in the left). In both methods--133Xe and DFW--coronary flow reserve was defined as the ratio of maximal hyperemic-to-baseline flow. DFW and 133Xe assessment of CFR correlated highly, whether adenosine was used i.c.(r=0.87; P=0.0001) or i.v.(r=0.78; P=0.0001). CFR obtained by DFW following i.c. and i.v. adenosine correlated well (r=0.79; P=0.0001). i.c. adenosine has fewer side effects. Both DFW and 133Xe are comparable in measuring CFR in humans.

Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators.

BACKGROUND: Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates. METHODS AND RESULTS: Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg x kg(-1) x h(-1) for 12 hours then 0.125 mg x kg(-1) x h(-1)), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg x kg(-1) x h(-1) for 12 hours then 0.25 mg x kg(-1) x h(-1)). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog, P=.023; heparin versus high-dose hirulog, P=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P<.01). CONCLUSIONS: Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.

Caution: prenatal clubfoot can be both a transient and a late-onset phenomenon.

Clubfoot (talipes equinovarus) is a common orthopaedic malformation that can be accurately diagnosed prenatally. The study was conducted to investigate possible in utero visualization of transient and late-onset clubfoot. Early (13-16 weeks' gestation) prenatal transvaginal sonographic diagnosis of clubfoot deformity was made in 36 cases during the study period. Only those cases where follow-up examination revealed different sonographic findings were considered. The results showed that seven cases of transient (as well as relapsing) clubfoot were identified. In 4 of 7 cases, the clubfoot resolved (all after more than 10 min of observation) during the same examination. In the fifth and sixth cases, it initially resolved, later reappearing in follow-up examinations (20 and 22 weeks' gestation). In the seventh case, the clubfoot persisted for two consecutive examinations (2 weeks apart each) and later disappeared. In addition, six late-onset (22-24 weeks' gestation) clubfoot cases were identified during the study period. Although infrequent, in utero clubfoot can be both a transient and a late-onset phenomenon. Over- and under-diagnosis are potential hazards in these situations.

Development of a whole platelet ELISA to detect circulating activated platelets.

P-selectin is a granule membrane protein that is expressed on the surface of activated endothelial cells and platelets. Flow cytometry has been used as a means of detecting activated platelets in the circulation by using antibodies to P-selectin and other surface markers. In the study reported here, we developed a whole platelet ELISA for measuring P-selectin on platelets in platelet-rich plasma. Platelet-rich plasma samples for analysis were isolated from fresh blood by centrifugation, fixed with 1.0% paraformaldehyde, and used within 3 hours or after storage at -70 degrees C for up to 10 months. Paraformaldehyde-fixed, phorbol myristate acetate-activated or thrombin receptor peptide-activated platelets were used to construct a standard calibration curve. These platelets were stable after 10 months of storage at -70 degrees C. Interassay variability showed a high degree of correlation, with r = 0.98 +/- 0.03 (n = 12). The accuracy and specificity of the ELISA was verified by using fluorescence-activated flow cytometric analysis and is as sensitive (< or = 0.5%) as flow cytometry for detecting P-selectin expression on platelets. To assess the ability of the platelet ELISA to detect platelet activation in the systemic circulation, we examined 24 patients with unstable angina and 12 age-matched control subjects. Patients with unstable angina demonstrated significantly higher levels of circulating activated platelets than did age-matched control subjects. Although storage-dependent differences in absolute platelet activation levels were found, platelet ELISA results of samples evaluated within either 3 hours or after 10 months of storage were comparable to results obtained by fluorescence-activated flow cytometric analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary air embolism: incidence, severity, and suggested approaches to treatment.

Because no well-controlled study of inadvertent coronary air embolism has been done to truly quantify the incidence of this cardiac catheterization complication, we wanted to determine its incidence and severity in an active teaching medical center and assess approaches to treatment. We retrospectively reviewed 3,715 coronary angiogram and PTCA reports performed over 32 months. Further, we classified severity based on angiographic findings and symptoms as minimal, mild, moderate, and massive. Two independent angiographers reviewed 764 consecutive cines performed in the first 2 months of training of each new fellow and 740 cines performed in the last 2 months of training. We found that during the first 2 months of training the overall incidence for significant intracoronary air embolism was 0.19% (7 documented cases) compared with 0.2% (3 cases) for non-reported, minimal asymptomatic air embolism. The estimated incidence for total air emboli events was 0.27% (10/3,715). We did not find coronary air emboli in the 740 cines performed at the end of fellowship training. Additionally, the incidence of coronary air emboli during PTCA training was much higher compared with coronary angiography training (0.84 vs. 0.24%). Although there is no best technique to restore blood flow after blockage by air emboli, we suggest as options aspirating the air or forcefully injecting saline, with auxiliary supportive measures like 100% oxygen, IABP, CPR, and DC cardioversion.

Percutaneous balloon aortic valvuloplasty in high-risk elderly patients.

From 1987 to mid-1994 we performed 16 percutaneous balloon aortic valvuloplasties. All patients (mean age 80 years; 53% female, 47% male) had significant congestive heart failure from aortic valve stenosis; the majority were categorized as New York Heart Association Class IV (shortness of breath at rest). Twelve patients were not surgical candidates; four patients refused surgery. After valvuloplasty, all patients became asymptomatic (NYHA Class I & II), the average preprocedure valvular gradient of 59 mm Hg decreased to 31 mm Hg, and valve area increased from 0.8 cm2 (0.3 cm2-0.98 cm2) to 1.3 cm2 (0.6 cm2-1.44 cm2). The only complications were two minor groin hematomas (2 patients). Within 6 months, 50% of the patients were symptomatic again; the overall survival rate was 23 months. We conclude that in the proper environment this procedure can be effective and safe--even in high-risk elderly patients. Although symptom improvement is transient, valvuloplasty provides a valuable opportunity to treat intercurrent medical conditions and possibly follow up with surgery.

Congenital clavicular pseudoarthrosis associated with vascular thoracic outlet syndrome: case presentation and review of the literature.

Thoracic outlet syndrome (TOS) associated with congenital clavicular pseudoarthrosis is rare in adults and often misdiagnosed. In this case report, we describe an adult female who was found to have thrombosis of the subclavian and axillary arteries with embolization documented by invasive angiography. This unusual vascular manifestation of TOS should remind physicians that anatomic derangements may predispose to upper extremity ischemia.