Silicon analysis of breast and capsular tissue from patients with saline or silicone gel breast implants: II. Correlation with connective-tissue disease

The silicone breast implant controversy rages on. Recent work has demonstrated that normal or baseline breast tissue silicon levels in women who had had no prior exposure to any type of breast implant may be as high as 446 microg/gm of tissue. These data ranged from 4 to 446 microg/gm of tissue, with a median of 27.0 microg/gm of tissue. In addition, numerous other epidemiologic and rheumatologic studies have demonstrated no association between silicone breast implants and any connective-tissue diseases. Despite these reports, the use of silicone implants remains restricted. The present study measured breast and capsular tissue silicon levels from 23 breasts in 14 patients with saline implants, and from 42 breasts in 29 patients with silicone implants. No patient in the saline implant group presented with signs or symptoms of connective-tissue disease. Patients with silicone implants, however, were divided into three groups based on the presence or absence of signs or symptoms of connective-tissue disease: group I, no symptoms or signs; group II, + symptoms, no signs; and group III, + symptoms, + signs. Six patients in group III were diagnosed with a specific connective-tissue disease, including systemic lupus erythematosus, rheumatoid arthritis, or scleroderma. The most common indications for implant removal or exchange were capsular contracture and implant rupture, although 41 percent of patients with silicone implants expressed media-related concern over the implant issue. The most common symptoms described by patients in groups II and III were joint pain and stiffness, arm pain and numbness, and fatigue. In all groups, capsular tissue silicon levels were significantly greater than breast tissue levels. This finding may indicate that the capsule serves as a barrier to the distribution of silicone from the implant into adjacent breast tissue. Although breast tissue silicon levels in patients with silicone implants were not significantly greater than those in patients with saline implants (p = 0.48), capsular tissue levels in patients with silicone implants were, indeed, significantly greater than those in patients with saline implants (p < 0.001). However, no statistically significant differences in tissue silicon levels were observed with relation to the presence or absence of connective-tissue disease signs or symptoms in patients with silicone implants (groups I to III). Therefore, these data strengthen the conclusion that there is no association between tissue silicon levels and connective-tissue disease.     

Genotype-phenotype analysis in four families with mutations in beta-myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy

The effects of two progestogen-only pills containing either 75 microgram desogestrel (DSG) or 30 microgram levonorgestrel (LNG) on hemostasis were investigated in a double-blind, randomized, controlled study of seven treatment cycles in 78 healthy women. DSG reduced factor VII activity (p < 0.05) and prothrombin fragment 1+2 (p < 0.05) and increased protein S (p < 0.001). LNG reduced factor VII activity (p < 0.01) and plasminogen activity (p < 0.01) and increased tissue-plasminogen activator (t-PA) (p < 0.05). At the end of the post-treatment cycle with DSG, protein S (p < 0.01) and t-PA (p < 0.05) were increased and plasminogen activity was decreased (p < 0.05), whereas with LNG, t-PA was increased (p < 0.001) and prothrombin fragment 1+2 (p < 0.05) and plasminogen activity (p < 0.001) were decreased. Between-group comparisons revealed higher values for DSG regarding the anticoagulatory parameter protein S at cycle 7 (p < 0.01) and post-treatment assessments (p < 0.05), and the fibrinolytic parameter plasmin-antiplasmin complex was higher with DSG at cycle 7 (p < 0.05) and at post-treatment (p < 0.05). Both preparations had comparable and potentially favorable effects of hemostasis, and may offer suitable hormonal contraception to women with a personal or family history of venous thromboembolic diseases.     

Differential item functioning in the Danish translation of the SF-36

Statistical analyses of Differential Item Functioning (DIF) can be used for rigorous translation evaluations. DIF techniques test whether each item functions in the same way, irrespective of the country, language, or culture of the respondents. For a given level of health, the score on any item should be independent of nationality. This requirement can be tested through contingency-table methods, which are efficient for analyzing all types of items. We investigated DIF in the Danish translation of the SF-36 Health Survey, using two general population samples (USA, n = 1,506; Denmark, n = 3,950). DIF was identified for 12 out of 35 items. These results agreed with independent ratings of translation quality, but the statistical techniques were more sensitive. When included in scales, the items exhibiting DIF had only a little impact on conclusions about cross-national differences in health in the general population. However, if used as single items, the DIF items could seriously bias results from cross-national comparisons. Also, the DIF items might have larger impact on cross-national comparison of groups with poorer health status. We conclude that analysis of DIF is useful for evaluating questionnaire translations.     

Antibiotic susceptibility profile of group B streptococcus acquired vertically

OBJECTIVE: To determine the contemporary antibiotic susceptibility profile of vertically acquired group B streptococcal isolates. METHODS: Susceptibility to ampicillin, penicillin G, erythromycin, clindamycin, cefazolin, and gentamicin was assessed by two methods, minimal inhibitory concentration and disc diffusion. RESULTS: The susceptibility profiles of 119 colonizing and eight invasive strains of group B streptococcus isolated from January 1996 to September 1997 at two hospitals in Birmingham, Alabama-University of Alabama at Birmingham and Cooper Green-were studied. Minimal inhibitory concentration determinations indicated that all colonizing strains were susceptible or moderately susceptible to ampicillin and penicillin G. Resistance was noted by at least one strain to each of the other antibiotics; all were resistant to gentamicin, whereas 27 (21%) were resistant to erythromycin, five (4%) to clindamycin, and one (1%) to cefazolin. All of the eight invasive strains were susceptible or moderately susceptible to ampicillin, penicillin G, clindamycin, and cefazolin; one (13%) was resistant to erythromycin, and all were resistant to gentamicin. Disc diffusion results generally were concordant with minimal inhibitory concentration results, although by disc diffusion fewer isolates were classified as susceptible, and more as moderately susceptible, to ampicillin and penicillin G than by minimal inhibitory concentration. CONCLUSION: Universal susceptibility of group B streptococcus to members of the penicillin family supports the continued use of penicillin G or ampicillin for early onset neonatal group B streptococcal disease prevention. For patients allergic to beta-lactam agents, clindamycin (4% resistance) may be a better alternative than erythromycin (21% resistance).     

Socioeconomic status, neighborhood social conditions, and neural tube defects

OBJECTIVES: This study evaluated the contributions of lower socioeconomic status (SES) and neighborhood socioeconomic characteristics to neural tube defect etiology. The influence of additional factors, including periconceptional multivitamin use and race/ethnicity, was also explored. METHODS: Data derived from a case-control study of California pregnancies from 1989 to 1991. Mothers of 538 (87.8% of eligible) case infants/fetuses with neural tube defects and mothers of 539 (88.2%) nonmalformed infants were interviewed about their SES. Reported addresses were linked to 1990 US census information to characterize neighborhoods. RESULTS: Twofold elevated risks were observed for several SES indicators. Risks were somewhat confounded by vitamin use, race/ethnicity, age, body mass index, and fever but remained elevated after adjustment. A risk gradient was seen with increasing number of lower SES indicators. Women with 1 to 3 and 4 to 6 lower SES indicators had adjusted odds ratios of 1.6 (1.1-2.2) and 3.2 (1.9-5.4), respectively, compared with women with no lower SES indicators. CONCLUSIONS: Both lower SES and residence in a SES-lower neighborhood increased the risk of an neural tube defect-affected pregnancy, with risks increasing across a gradient of SES indicators.     

Scaling of movement velocity: a measure of neuromotor retardation in individuals with psychopathology

The combination of ifosfamide, carboplatin and etoposide (modified ICE), was evaluated for its toxicity and activity in relapsed or refractory aggressive non-Hodgkin's lymphoma. Twenty patients, 14-69 years of age, with relapsed (19 cases) or refractory (one case) aggressive non-Hodgkin's lymphoma were treated with modified ICE therapy, consisting of ifosfamide 6 g/m2 (1.2 g/m2 day 1-5), carboplatin 400 mg/m2 (day 1) and etoposide 500 mg/m2 (100 mg/m2 day 1-5). The regimen was repeated at approximately 28-day intervals. All patients had undergone a doxorubicin-containing regimen before modified ICE therapy. Median total dose of previously received doxorubicin was 406 mg/m2 (range: 200-825 mg/m2). The median interval from diagnosis to modified ICE therapy was 9.4 months (range: 3.6-121 months). Two patients achieved CR and five achieved PR out of 16 patients with measurable lesions (response rate 43.8%; 95% confidence interval 19.0-68.6%). Median overall survival was 227 days (range: 41-552 days) from the start of modified ICE therapy. Myelosuppression was the most serious toxicity, namely 16 patients (80%) and 11 patients (55%) showed grade 4 neutropenia and grade 4 thrombocytopenia after the first course, respectively. Modified ICE therapy might be an active regimen with acceptable toxicity as a salvage chemotherapy in aggressive non-Hodgkin's lymphoma.     

The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4

The Transforming Growth Factor-beta superfamily member decapentaplegic (dpp) acts as an extracellular morphogen to pattern the embryonic ectoderm of the Drosophila embryo. To identify components of the dpp signaling pathway, we screened for mutations that act as dominant maternal enhancers of a weak allele of the dpp target gene zerkn?llt. In this screen, we recovered new alleles of the Mothers against dpp (Mad) and Medea genes. Phenotypic analysis of the new Medea mutations indicates that Medea, like Mad, is required for both embryonic and imaginal disc patterning. Genetic analysis suggests that Medea may have two independently mutable functions in patterning the embryonic ectoderm. Complete elimination of maternal and zygotic Medea activity in the early embryo results in a ventralized phenotype identical to that of null dpp mutants, indicating that Medea is required for all dpp-dependent signaling in embryonic dorsal-ventral patterning. Injection of mRNAs encoding DPP or a constitutively activated form of the DPP receptor, Thick veins, into embryos lacking all Medea activity failed to induce formation of any dorsal cell fates, demonstrating that Medea acts downstream of the thick veins receptor. We cloned Medea and found that it encodes a protein with striking sequence similarity to human SMAD4. Moreover, injection of human SMAD4 mRNA into embryos lacking all Medea activity conferred phenotypic rescue of the dorsal-ventral pattern, demonstrating conservation of function between the two gene products.     

Medical marijuana

To evaluate the use of high-resolution magnetic resonance imaging (MRI) for the differentiation of skin tumors in the maxillofacial region, 60 patients (25 female) were examined in a 1.5-T whole-body MR imager with a 2.5-cm surface coil. Plain transverse T1-(TR 500 ms, TE 25 ms), T2-(2200 ms, TE 80 ms), fat-(TR 500 ms, TE 28 ms), and water-suppressed (TR 500 ms, TE 38 ms) SE sequences were used. Following the application of the paramagnetic contrast agent Gd-DTPA, transverse T-weighted and fat suppression sequences were repeated. Before and after contrast administration, tumor signal intensities and percent contrast enhancement were determined by a ROI technique. All tumors were classified by standard histologic technique and evaluated with regard to their response to contrast medium. Quantitative evaluation was performed by three independent radiologists. Additionally, signal- and contrast-to-noise ratios were calculated for each tumor type. All MRI findings were compared with histology. Significant contrast enhancement occurred in most tumors; malignant tumors displayed inhomogeneous enhancement. The optimal pulse sequences for tumor delineation are plain T1-weighted, water-suppressed, and contrast-enhanced fat-suppressed sequences. Tumors could not be specified by signal intensities or percent contrast enhancement, and CNR did not allow for malignant lesions to be differentiated from benign tumors. High-resolution MRI proved to be an adequate method for imaging skin tumors and their inner structure. Tumor typing was not possible by either contrast-administration or modification of sequence parameters. In this regard, further innovations in contrast agent design seem to be necessary.