Role of preoperative plasma CA 15-3 and carcinoembryonic antigen levels in determining histopathologic conventional prognostic factors for breast cancer

Abstract Breast cancer is one of the leading causes of cancer death among women all over the world, with about one million new breast cancer cases diagnosed per year. This large number of cases make the diagnosis, treatment, and determination of the factors affecting the survey extremely important. The aim of this study was to evaluate the importance of the preoperative plasma CA 15-3 and carcinoembryonic antigen (CEA) levels when determining the conventional histopathologic prognostic factors (tumor grade, lymphatic infiltration, stromal invasion, vessel invasion, tumor necrosis, elastosis, and number of positive lymph nodes in levels I and II). We believe that with this protocol doctors can add to their knowledge about the prognosis of patients. After examining the serum tumor marker levels and the histopathology results of 29 patients and submitting them to statistical calculations, we strongly believe that preoperative serum CA 15-3 levels can be taken into consideration when evaluating the prognosis because the CA 15-3 level is directly and positively correlated with the gold standard prognostic factor: the number of level I and II positive lymph nodes. Electronic Publication     

The relation between tooth loss and bone mass in postmenopausal osteoporotic women in Turkey: a multicenter study

 The purpose of this study was to investigate the associations of tooth loss with skeletal bone mass, years since menopause, educational level, current smoking status, dietary calcium intake, and number of pregnancies in postmenopausal osteoporotic women in Turkey. The study population consisted of 1171 postmenopausal women aged 40–86 years (mean age, 61.19 ± 7.28 years). A detailed history was obtained from all women, including relevant lifestyle parameters, risk factors, and measurements of weight and height. Women were separated into three groups according to the number of teeth remaining as group 1 (edentulous, 457 women), group 2 (10 or fewer teeth, 232 women), and group 3 (more than 10 teeth remaining, 482 women). There was no significant difference among the three groups in mean age and menopausal age (P < 0.05). Body mass index of group 1 was significantly higher than that of group 2 (P < 0.01). Educational level was significantly different between three groups: groups 1 and 2 (P < 0.001), groups 1 and 3 (P < 0.0001), and groups 2 and 3 (P < 0.001). Educational level was lowest in group 1 and highest in group 3. Despite a low ratio of cigarette smoking in general, a smoking habit was most prevalent in group 3 and least in group 2. The ratio of women receiving adequate calcium was significantly lower in group 1 than in other groups (P < 0.001); mean calcium intake was similar in all groups. The number of pregnancies was significantly higher in group 1 than in other groups (P < 0.001). Lumbar bone mineral density (BMD) of group 1 was significantly lower than that of groups 2 and 3 (P < 0.001). Although no significant difference was found between groups 1 and 3, femoral neck BMD of group 2 was less than in others, and differences between groups 1 and 2 and between groups 2 and 3 (P < 0.001) were significant. Lumbar bone mineral content (BMC) of group 1 was significantly lower than that of groups 2 and 3 (P < 0.001), and lumbar BMC in group 2 was significantly higher than in group 3 (P < 0.05). Femoral neck BMC in group 1 was significantly higher than in groups 2 and 3 (P < 0.001). In conclusion, lumbar BMD and BMC in the edentulous group were significantly lower, whereas femoral neck BMD and BMC were significantly higher in edentulous group compared with the others. Our findings indicated that improvement in lifestyle factors and nutritional strategies for the treatment and prevention of osteoporosis may have additional benefit in reducing tooth loss. Received: February 18, 2002 / Accepted: June 21, 2002 Offprint requests to: A. Gur     

Influence of number of pregnancies on bone mineral density in postmenopausal women of different age groups

 As data on the relationship between parity and bone mineral density often seem to be controversial, ultimately, a comprehensive research study was thought to be necessary. This study focused on examining the influence of the number of pregnancies on bone mineral density and investigating the relationship between pregnancy and bone mineral density at four sites in postmenopausal women of different age groups. A total of 509 postmenopausal women, varying from 45 to 86 years of age (mean age of 60.85 ± 7.53 years) were considered for the study. A standardized interview was employed to obtain information on demographics, lifestyle, and, reproductive and menstrual histories. Patients were separated into four groups according to the number of pregnancies, i.e., nulliparae (52 patients), one to two parity (66 patients), three to five parity (178 patients), and more than five parity (213 patients). The patients were further classified into two age groups, 40–59 years (233 patients) and 60–80 years (276 patients), respectively. The number of pregnancies was found to range from 0 to 17 (with an overall mean of 5.42 ± 3.68), with 4.29 ± 2.74 (range, 0–16) accounting for live births, while 1.02 ± 1.53 (range, 0–14) were abortions. There were no significant differences among the groups with respect to parameters such as, age, body mass index (BMI), age at menarche, age at menopause, and years since menopause (P > 0.05) in all of the 509 women and in the 40- to 59- and 60- to 80-year groups. When all the patients were considered, the bone mineral density (BMD) values of the spine and the trochanter for the more-than-five-parity group, were found to be significantly lower than those of the other groups (P < 0.05), while the BMD values of the spine and the femur (neck, trochanter) appeared to decrease with increasing parity. In the 40- to 59-year group, the BMD of the spine in both the nulliparae and one-to-two-parity groups was significantly higher than that of the more-than-five-parity group (P < 0.05). No significant differences were found among the groups with respect to the BMD values at any femur sites. The nulliparae patients in the 60- to 80-year group exhibited significantly higher trochanter and Ward's BMD values than those of the more-than-five-parity group (P < 0.05), whereas in the one-to-two-parity group, spine BMD values appeared to be significantly higher than those of the more-than-five-parity group (p < 0.05). Significant correlations were found between the number of pregnancies and BMD values for the spine (r = −0.23; P < 0.01), trochanter (r = −0.16; P < 0.01), and Ward's triangle (r = −0.14; P < 0.05), with no significant correlation for femur neck BMD (r = −0.08; P > 0.05) values. In conclusion, the present study suggests that the number of pregnancies has an effect on the BMD values and that this situation shows a variation in different age groups. In addition, our study indicates that there is a significant correlation between the number of pregnancies and the spine, trochanter, and Ward's triangle BMD, but there is no correlation for the femur neck BMD. Received: April 30, 2002 / Accepted: January 16, 2003 RID="*" ID="*" Offprint requests to: A. Gur     

Surveillance of Haemophilus influenzae among respiratory tract samples of Turkish children

We conducted three prospective studies of Haemophilus influenzae in different groups of children. Pharyngeal swab samples were taken (i). from 1382 healthy infants and children between 0 and 10 years of age (group 1), attending well child clinics (n=438), day care centres (n=440) and elementary schools (n=504), and (ii). from 322 children aged 2-10 years (group 2), clinically diagnosed as having upper respiratory tract infection. Pharyngeal swab samples and sinus aspirates were obtained from 49 children between 2 and 9 years of age (group 3), clinically diagnosed as having sinusitis. H. influenzae was isolated in similar rates from 315 (22.7%) of children in group 1, 72 (22.3%) of children in group 2 and 12 (24.4%) of children in group 3. Serotype b comprised 7, 5.2 and 2% of all H. influenzae isolates for group 1, 2 and 3, respectively. Production of beta-lactamase was detected in 1.0% of H. influenzae type b isolates in group 1, 1.2 and 6.1% of all isolates in group 2 and 3, respectively. There were no beta-lactamase negative ampicillin-resistant strains.     

Cell proliferation and apoptosis are altered in mice deficient in the NF-kappaB p50 subunit after treatment with the peroxisome proliferator ciprofibrate.

We previously showed that the peroxisome proliferator ciprofibrate increases hepatic NF-kappaB DNA binding activity in rats, mice, and hepatoma cell lines. Here, we analyzed the response to ciprofibrate in mice that lack the NF-kappaB p50 gene (p50-/-). Wild-type and p50-/- mice were fed a diet with or without 0.01% ciprofibrate for 10 days. NF-kappaB DNA binding activity was present and increased after ciprofibrate treatment in wild-type mice, but was not detected in p50-/- mice. The untreated p50-/- mice had a higher level of hepatic cell proliferation, as measured by BrdU labeling, than did untreated wild-type mice. However, the increase in proliferation was greater in ciprofibrate-fed wild-type mice than in ciprofibrate-fed p50-/- mice. The apoptotic index was low in wild-type mice in the presence or absence of ciprofibrate. Apoptosis was increased in untreated p50-/- mice compared to wild-type mice; apoptosis was reduced in p50-/- mice after ciprofibrate feeding. The c-Jun and JunB mRNA levels were higher in untreated p50-/- mice than in untreated control mice; c-Jun mRNA levels increased, whereas JunB mRNA levels decreased in both groups after ciprofibrate treatment. The c-Jun and JunB protein levels were the same in untreated wild-type and p50-/- mice and increased in both groups after ciprofibrate treatment. Several apoptosis-related mRNAs were higher in untreated p50-/- mice compared to untreated control mice; expression of these genes increased in both groups after ciprofibrate treatment. These data indicate that NF-kappaB contributes to the proliferative and apoptotic changes that occur in the liver in response to ciprofibrate.     

Vaccines and animal models for arboviral encephalitides

Arthropod-borne viruses (“arboviruses”) cause significant human illness ranging from mild, asymptomatic infection to fatal encephalitis or hemorrhagic fever. The most significant arboviruses causing human illness belong to genera in three viral families, Togaviridae, Flaviviridae, and Bunyaviridae. These viruses represent a significant public health threat to many parts of the world, and, as evidenced by the recent introduction of the West Nile virus (WNV) to the Western Hemisphere, they can no longer be considered specific to any one country or region of the world. Like most viral diseases, there are no specific therapies for the arboviral encephalitides; therefore, effective vaccines remain the front line of defense for these diseases. With this in mind, the development of new, more effective vaccines and the appropriate animal models in which to test them become paramount. In fact, for many important arboviruses (e.g. California serogroup and St. Louis encephalitis viruses), there are currently no approved vaccines available for human use. For others, such as the alphaviruses, human vaccines are available only as Investigational New Drugs, and thus are not in widespread use. On the other hand, safe and effective vaccines against tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JEV) have been in use for decades. New challenges in vaccine development have been met with new technologies in vaccine research. Many of the newer vaccines are now being developed by recombinant DNA technology. For example, chimeric virus vaccines have been developed using infectious clone technology for many of the arboviruses including, WNV, JEV, and TBEV. Other successful approaches have involved the use of naked DNA encoding and subsequently expressing the desired protective epitopes. Naked DNA vaccines have been used for TBEV and JEV and are currently under development for use against WNV. The development of less expensive, more authentic animal models to evaluate new vaccines against arboviral diseases will become increasingly important as these new approaches in vaccine research are realized. This article reviews the current status of vaccines, both approved for use and those in developmental stages, against the major arboviral encephalitides causing human disease. In addition, research on animal models, both past and present, for these diseases are discussed.     

Limits to the safety net: teaching hospital faculty report on their patients' access to care

Many major teaching hospitals might not be able to offer adequate access to specialty care for uninsured patients. This study found that medical school faculty were more likely to have difficulty obtaining specialty services for uninsured than for privately insured patients. These gaps in access were similar in magnitude for public and private institutions. Initial treatment of uninsured patients at academic health centers (AHCs) does not guarantee access to specialty and other referral services, which suggests that there are limits to relying on a health care safety net for uninsured patients. AHCs and affiliated group practices should examine policies that limit access for uninsured patients.     

Identification of communicating branches among the dorsal,perineal and cavernous nerves of the penis

PURPOSE: The mechanism of human erection requires the coordination of an intact neuronal system that includes the cavernous, perineal, and dorsal nerves of the penis. We defined the communication of these 3 nerves that travel under the pubic arch using specific neuronal immunohistochemical staining and 3-dimensional reconstruction imaging technique. MATERIALS AND METHODS: A total of 18 normal human fetal penile specimens at 17.5 to 32 weeks of gestation were studied by immunohistochemical techniques. Serial sections were stained with antibodies raised against the neuronal markers S-100, and neuronal nitric oxide synthase (nNOS), vesicular acetylcholine transporter (VAChT), calcitonin gene-related peptide and substance P. RESULTS: The continuation of the dorsal neurovascular bundle of the prostate was documented under the pubic arch. Two distinct nerve bundles were identified superior to the urethra and medial to the origin of the crural bodies. Nerve bundles were observed to join the corporeal bodies at the penile hilum. Proximal to the penile hilum the dorsal nerves stained only for S-100 and VAChT. From the junction of the crural bodies at the hilum to the glans penis dorsal nerve fibers stained positive for S-100, VAChT and nNOS. Calcitonin gene-related peptide and substance P demonstrated positive staining at the distal nerves, particularly at the glans. In contrast, the whole course of the cavernous nerve stained for S-100 and nNOS. Under the pubic arch at the penile hilum the cavernous nerves were found to convey nNOS positive branches to the dorsal nerve to transform its immunoreactivity to nNOS positive. Proximal nNOS negative perineal nerves were shown to stain positive for nNOS distal on the penis. Interaction between nNOS positive dorsal nerve branches and perineal nerves was at the cavernous-spongiosal junction, where the bulbospongiosus muscle terminates. CONCLUSIONS: At penile hilum, where the corporeal bodies start to separate, the cavernous nerve sends nNOS positive fibers to join the dorsal nerve of the penis, thereby, changing the functional characteristics of the distal penile dorsal nerve. Similarly the nNOS negative, ventrally located perineal nerve originating from the pudendal nerve becomes nNOS reactive at the cavernous-spongiosal junction. These 2 examples of redundant neuronal wiring in the penis may impact erectile function, especially during reconstructive surgery.     

Automated quantification of apoptosis after neoadjuvant chemotherapy for breast cancer: early assessment predicts clinical response.

PURPOSE: A large body of evidence implicates apoptosis in the effects of cancer chemotherapeutic agents on tumor cells in vitro and tumor xenografts in vivo, but the predictive value of apoptosis as an early marker for clinical response in cancer patients remains unclear. EXPERIMENTAL DESIGN: We developed an automated, laser scanning cytometer-based method to quantify the percentage of tumor cells containing DNA fragmentation characteristic of apoptosis in tumor sections. We measured levels of apoptosis in a panel of 15 matched, 18-gauge core breast cancer biopsies obtained before and 48 h after neoadjuvant therapy with docetaxel plus doxorubicin or paclitaxel as part of two prospective clinical trials. RESULTS: The results revealed a strongly significant (P = 0.0023) association between chemotherapy-induced apoptosis and pathological response. CONCLUSIONS: If the results can be validated in a larger patient cohort, the method could be used to "tailor" therapy to optimize benefit in a patient-specific fashion.     

Feto-maternal morbidity and mortality after cardiac valve replacement

BACKGROUND: The aim of this study is to evaluate the fetomaternal morbidity and mortality of the pregnancies of women who conceived after cardiac valve replacement. METHODS: A consecutive series of one hundred and thirty-six pregnancies of one hundred and one patients who conceived after cardiac valve replacement were retrospectively analyzed. Regarding the anticoagulation therapy, 101 patients were classified into three groups: A: patients on oral anticoagulants (n=68), B: patients on heparin (n=16) and C: patients who received no anticoagulation (n=17). RESULTS: Three groups (patients on oral anticoagulants (A), on heparin (B), patients who received no anticoagulation (C)) were compared in terms of spontaneous abortion (19%, 11%, 5.6%), preterm delivery (14%, 22.3%, 16.6%), maternal mortality (3%, 11.1%, 0%), thromboembolic events (4%, 11.1%, 0%), cardiac failure (6%, 11.1%, 11.1%), atrial fibrillation (9%, 11.1%, 5.6%), antenatal bleeding (9%, 11.1%, 5.6%), delivery route and fetal malformation (5%, 0%, 0%) and no statistically significant differences were detected. In group B, hematoma formation rate (22.2%) (p=0.011) and transfusion rate (27.8%) (p=0.005) were significantly higher. Five cases of congenital anomalies were detected, all belonging to group A, but this tendency was not found to be statistically significant. CONCLUSIONS: Management of pregnancies with prosthetic heart valves require closely monitored anticoagulation, and an obstetrician should be familiar with the potential fetal and maternal adverse effects of any anticoagulant therapy during the course of pregnancy.