Tamoxifen aziridine binding to cytosolic proteins from human breast specimens is negatively associated with estrogen receptors, progesterone receptors, pS2, and cathepsin-D

[³H]Tamoxifen Aziridine ([³H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [³H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [³H]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [³H]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [³H]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/mg p.). The 4S peak of [³H]TAZ was partially inhibited by both estrogens and antiestrogens. When [³H]E₂ was used instead of [³H]TAZ, only an 8S peak was detected. [³H]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [³H]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [³H]TAZ binding was not associated with clinico-pathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [³H]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [³H]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.     

Visual inspection with acetic acid for cervical cancer screening outside of low-resource settings.

OBJECTIVES: To assess visual inspection with acetic acid (VIA) as a screening tool for use in a well-equipped health center in Peru, to evaluate VIA as an alternative or adjunct to the Papanicolaou (Pap) smear, and to determine if VIA can play a role in settings other than low-resource ones. METHODS: This was a prospective study of 1 921 asymptomatic women living in Lima, Peru, carried out in 1999 and 2000. The study was performed at a cancer center equipped with the latest-generation technology and highly trained oncologists. The women underwent a complete clinical evaluation, including a Pap smear and VIA. Participants with any positive test were referred for colposcopy and biopsy. RESULTS: More women tested positive by VIA than on the Pap smear (6.9% vs. 4.2%; P = 0.0001). There were 35 women with histologic cervical intraepithelial neoplasia grade 1 (CIN 1); of these, 15 were detected by Pap and 20 by VIA (P = 0.4). A diagnosis of CIN 2 or 3 (CIN 2-3) was confirmed in a total of 13 cases; Pap detected 5 of the cases and VIA 11 of the cases (P = 0.06). The positive predictive value for detection of CIN 2+ was 8.3% for VIA and 6.3% for Pap (P = 0.5). Most importantly, while only 2.3% of patients with a positive VIA were lost to follow-up before colposcopy, that was true for 26.3% of the women with a positive Pap smear (P < 0.0001). CONCLUSIONS: VIA is useful for detection of precursor lesions of cervical cancer not only in low-resource settings but also in well-equipped health centers and cancer centers. In these non-low-resource settings, VIA has a positive predictive value comparable to the conventional Pap smear, but it is more likely to achieve earlier diagnosis, follow-up, and treatment than cytology-based screening.     

Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the population of Santiago (Chile) using a Total Diet Study.

Dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Santiago (Chile) was determined using a Total Diet Study in the market basket modality. After conducting a survey of the foods consumed in the last 24 h, the most consumed food products were included in the basket. Subsequently, they were cooked or prepared according to typical Chilean procedures and grouped into 17 food categories according to their chemical characteristics. The fish and shellfish group had the highest contents of As (1351 ng/g wet weight, ww), Cd (277 ng/g ww), and Hg (48 ng/g ww), while the sugar group had the highest content of Pb (251 ng/g ww). For a person with a body weight of 68 kg, the dietary intakes of As (77 microg/day), Cd (20 microg/day), Hg (5 microg/day), and Pb (206 microg/day) are lower than the provisional tolerable weekly intake values established by the FAO/WHO. Consequently, the total intakes of As, Cd, Hg, and Pb in Santiago (Chile) are within the limits estimated as safe.     

Severe incisional pain and long thoracic nerve injury after port-access minimally invasive mitral valve surgery

The authors describe the occurrence of severe postoperative pain and long thoracic nerve injury after Port-Access minimally invasive mitral valve surgery. The potential for these events and the impact on postoperative hospitalization and rehabilitation are emphasized.     

Clinical Impact of 18F-FDG-PET in the Suspicion of Recurrent Ovarian Carcinoma Based on Elevated Tumor Marker Serum Levels

Purpose: To retrospectively evaluate the contribution of 18F-fluorodeoxy-glucose-positron emission tomography (FDG-PET) to the diagnosis and clinical management of patients who were suspected of recurrent ovarian carcinoma, based on elevated tumor markers levels with normal or equivocal computed tomography (CT) or nuclear magnetic resonance (NMR).Procedures: 20 patients with these characteristics underwent FDG-PET. PET findings were confirmed in 14, in 7 by surgery, and in the other 7 by clinical course.Results: Recurrence was confirmed in 12 patients, all with FDG-PET positive. In other 2, recurrence was rule out and in 1, FDG-PET was negative. FDG-PET accuracy was 93% with 4 surgeries avoided and guided other 6.Conclusions: FDG-PET is an useful technique for detecting recurrent ovarian carcinoma suspected by elevated tumor markers levels and normal or equivocal results in the morphologic imaging techniques and has an important clinical impact on the management of these patients.     

Treatment of osteoarthritis of the knee with valgus deformity by means of varus osteotomy

Nineteen cases of osteoarthritis of the knee with valgus deformity in 17 patients were treated by femoral supracondylar varus osteotomy (17 cases) or by high tibial varus osteotomy (2 cases) over the last 15 years. Fixation was performed using a 95 degrees AO blade-plate in 13 of the femoral osteotomies and a straight plate in the other four. The mean follow-up time was 6.5 years. The valgus deformity was idiopathic in 14 cases, secondary to rheumatoid arthritis in 2 cases and to tibial valgus in one case. The Hospital for Special Surgery (HSS) score was used to evaluate the clinical results: nearly 75% were excellent or good. The causes related to poor results are analyzed regarding indication and surgical technique. It appears that varus osteotomy is an effective procedure for the treatment of osteoarthritis of the knee with valgus deformity, above all in order to alleviate pain, although the operation requires precision, and correct selection of patients is of prime importance.     

Treatment of proximal hypospadias with a tubularized island flap urethroplasty and the onlay technique: a comparative study

BACKGROUND/PURPOSE: The onlay island flap urethroplasty was first described in the repair of mid and distal penile hypospadias. Since then, this technique has been increasingly used in more severe cases of hypospadias, because of the complications of tubularized flaps, mainly megaurethra and proximal anastomotic strictures. The aim of this study was to compare the morbidity of these 2 techniques. METHODS: Between April 1994 and December 1998, 80 patients underwent surgical treatment for hypospadias. A tubularized island flap (Ducketttechnique) was performed in 42 cases, and the onlay island flap technique was used in 38 patients. The authors retrospectively compared the complication rate and type of these 2 procedures. RESULTS: Altogether, fistula was the most frequent complication without any significant difference between the 2 groups (21.4% for Duckett technique and 18.4% for onlay repair; P > .05). However, the anastomotic stricture was much more common in the tubularized flap group (7.14% v 2.63%; P < .05). Moreover, a megaurethra was found only in the Duckett technique group (4.7%). There was no case of chordee recurrence, but 6 patients (15.7%) treated with the onlay technique required urethrolysis including dissection of the chord behind the urethral plate, and in the other 3 patients of the same group (7.9%), a dorsal Nesbit plication also was necessary. In all these cases, the urethroplasty included an island cutaneous flap to provide ventral coverage to the neourethra. CONCLUSIONS: The authors conclude that both techniques present similar complications. However, proximal strictures and megaurethra are more common after the Duckett technique. This procedure is of choice in patients with scrotal hypospadias. Conversely, the onlay repair should be completed with other procedures (urethrolysis, dorsal Nesbit plication) to obtain good results in patients with severe degree of chordee.     

Satisfaction with provider communication among Spanish-speaking Medicaid enrollees.

OBJECTIVE: To determine if differences between English- and Spanish-speaking parents in ratings of their children's health care can be explained by need for interpretive services. METHODS: Using the Consumer Assessment of Health Plans Survey-Child-Survey (CAHPS), reports about provider communication were compared among 3 groups of parents enrolled in a Medicaid managed care health plan: 1) English speakers, 2) Spanish speakers with no self-reported need for interpretive services, and 3) Spanish speakers with self-reported need for interpretive services. Parents were asked to report how well their providers 1) listened carefully to what was being said, 2) explained things in a way that could be understood, 3) respected their comments and concerns, and 4) spent enough time during medical encounters. Multivariate logistic regression was used to compare the ratings of each of the 3 groups while controlling for child's gender, parent's gender, parent's educational attainment, child's health status, and survey year. RESULTS: Spanish-speaking parents in need of interpretive services were less likely to report that providers spent enough time with their children (odds ratio = 0.34, 95% confidence interval = 0.17-0.68) compared to English-speaking parents. There was no statistically significant difference found between Spanish-speaking parents with no need of interpretive services and English-speaking parents. CONCLUSIONS: Among Spanish- versus English-speaking parents, differences in ratings of whether providers spent enough time with children during medical encounters appear to be explained, in part, by need for interpretive services. No other differences in ratings of provider communication were found.     

Peripheral nervous system neurotoxicity secondary to chemotherapy treatment]

Peripheral neurotoxicity is a crucial side effect of chemotherapeutic agents. It is the only situation where there is no preventive treatment. Neuromuscular toxicity has become the major dose limiting side effect for many chemotherapeutic agents. The iatrogenic toxic neuropathy is a growing neurologic problem, as cancer patients are beign treated with increasing doses of chemotherapy drugs. Major advances in cancer treatment have resulted from the use of drug combinations; for some combinations this raises the possibility of sinergistic neurotoxicity. The following report reviews the SNP toxicities encountered with cisplatin, vincristine, taxanes and others, and methods to minimize the deleterious effect of chemotherapeutic agents.