Totally implantable active middle-ear implants: a large, single-surgeon cohort.

OBJECTIVES: This study aimed to evaluate hearing outcomes and device safety in a large, single-surgeon experience with the totally implantable active middle-ear implants. METHODS: This was a retrospective case series review of 116 patients with moderate-to-severe sensorineural hearing loss undergoing implantation of active middle-ear implants. RESULTS: Mean baseline unaided pure tone average improved from 57.6 dB before surgery to 34.1 dB post-operatively, signifying a mean gain in pure tone average of 23.5 dB (p = 0.0002). Phonetically balanced maximum word recognition score improved slightly from 70.5 per cent to 75.8 per cent (p = 0.416), and word recognition score at a hearing level of 50 dB values increased substantially from 14.4 per cent to 70.4 per cent (p < 0.0001). Both revision and explant rates were low and dropped with increasing surgeon experience over time. CONCLUSION: This study showed excellent post-operative hearing results with active middle-ear implants with regard to pure tone average and word recognition score at a hearing level of 50 db. Complication rates in this case series were significantly lower with increasing experience of the surgeon. Active middle-ear implants should be considered in appropriate patients with moderate-to-severe sensorineural hearing loss who have struggled with conventional amplification and are good surgical candidates.

Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial.

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

False positive newborn screening results are not always benign.

OBJECTIVE: Our goal was to assess the impact on families of receiving abnormal newborn screening results. PATIENTS AND METHODS: We conducted telephone interviews with parents of 3 groups of children who had received abnormal newborn screening results: (1) false positive but otherwise healthy (FP, n = 28), (2) true positive (TP, n = 20), and (3) false positive with other medical conditions (FP + other, n = 12). Interviews, based on the instruments developed by Waisbren et al. [J Pediatr Psychol 2004;29:565-570], included open- and close-ended questions as well as the Parental Stress Index (PSI). RESULTS: In response to open ended questions, FP parents expressed concern about having more children and identified numerous problems with how they were told about newborn screening. Parents of FP + other reported the most stress, followed by parents of children with metabolic disease. Nonetheless, almost 10% of FP parents reported clinically significant stress as well as worry about their child's health and future. CONCLUSIONS: False positive newborn screening results cause some parents to experience stress and long-term worry. Although more work is needed to learn how well these sequelae can be averted by more effective communication in the pre- and postnatal periods, these effects need to be considered in deciding whether to add new disorders to newborn screening panels.

Percutaneous tumor ablation: microencapsulated echo-guided interstitial chemotherapy combined with cryosurgery increases necrosis in prostate cancer.

This study aimed at confirming the increased growth inhibition (GI) of human prostate tumors produced by a intentionally palliative combination treatment of cryochemotherapy, i.e., partial cryoablation (CA) followed by intratumor partial chemotherapy with injection of microencapsulated 5-fluorouracil (MCC/5FU) at the ice ball (IB) periphery. We report the local effectiveness of cryochemotherapy compared to chemotherapy only with using multiple injections of MCC/5FU spaced out to maximize cumulative effect of sustained release of 5-fluorouracil (5FU) during a 21-day period. Prostate bioluminescent tumor cells - DU145 Luc+ - were implanted sub-cutaneously and bilaterally in each flank of nude mice. Tumors were treated with: (i) cryoablation alone (CA), causing necrosis in approximately 45% of the tumor volume; (ii) cryo-chemotherapy (CA+MCC/5FU), a combined regimen consisting of partial CA followed immediately and on day 14 by ultrasound assisted, intra-tumor injections (40 mul) of MCC/5FU( 0.81 ng/mm3 of tumor) containing Ethiodol (IPO) an imaging contrast agent, on two opposite sides of the unfrozen part of tumor; (iii) intratumor chemotherapy (MCC/5FU), consisting of three successive intra-tumor injections of microencapsulated 5FU on two opposite sides on Day 0, 4, and 11, and (iv) control series (MM), consisting of a single injection of echogenic microcapsules (mucaps) containing IPO but no 5FU. Tumor growth and viability were followed during a 21-day period with using biometric measurements, bioluminescent imaging (BLI) and ultrasonography (US), and then animals were sacrificed. CA, spared 54.4% of the tumor volume and the IB kill ratio was 0.4 +/-0.9. The maximum tumor volume reduction observed by Day 3 was short-lived as re-growth became significant by Day 6. CA+ MCC/5FU spared 55.6% of the tumor volume and the IB kill ratio was 0.54 +/- 0.12. The viable tumor cells, as measured by BLI remained at preoperative levels. After 11 days CA+ MCC/5FU limited the growth of the partially ablated tumors to only 10.6% of the growth of CA treated tumors (p=0.04). By Day 18 the CA+MCC/5FU had inhibited tumor growth by 78% compared to the CA treated tumors (p=0.05) and after 21 days the growth was inhibited by 71% (p=0.04) compared to more than 650% growth in the MM group and 600% growth in the CA treated group. The two injections of MCC/5FU produced a visible focal necrosis in 55% of the tumors. MCC/5FU proved effective by themselves and reduced the growth of prostate tumor volumes by 51% (p=0.025) compared to MM controls during the 21 days. Focal necrosis was macroscopically visible at the site of 66% of the tumors injected only with MCC/5FU. The BLI clearly showed zones of reduced tumor cell viability at the injection sites. The mean number of bioluminescent (viable) tumor cells, remained below preoperative levels for the first 6 days and then increased at a rate approximately 20% that of the growth of control tumor cells. The chemoablative effects of intentionally limited doses of MCC/5FU injected within the IB margin augment the effects of incomplete cryoablation in this prostate tumor model, with dramatic tumor GI and directionally increased necrosis dimensions compared to CA alone, confirming the results of a previous study. Our results indicate the potential advantages of our combination cryochemotherapy that utilizes different mechanisms to kill tumor cells and retard tumor growth in the region surrounding the IB where tumor cells escape the lethal effects of cryosurgery. The study suggests that cryochemotherapy may become a more predictable technique that could be indicated as an adjuvant or an alternative to palliative therapy of hormone refractory prostate cancer (HRPC).

Electrophoresis in space.

Programs for free flow electrophoresis in microgravity over the past 25 years are reviewed. Several studies accomplished during 20 spaceflight missions have demonstrated that sample throughput is significantly higher in microgravity than on the ground. Some studies have shown that resolution is also increased. However, many cell separation trials have fallen victim to difficulties associated with experimenting in the microgravity environment such as microbial contamination, air bubbles in electrophoresis chambers, and inadequate facilities for maintaining cells before and after separation. Recent studies suggest that the charge density of cells at their surface may also be modified in microgravity. If this result is confirmed, a further cellular mechanism of "sensing" the low gravity environment will have been found. Several free fluid electrophoresis devices are now available. Most have been tried at least once in microgravity. Newer units not yet tested in spaceflight have been designed to accommodate problems associated with space processing. The USCEPS device and the Japanese FFEU device are specifically designed for sterile operations, whereas the Octopus device is designed to reduce electroosmotic and electrohydrodynamic effects, which become dominant and detrimental in microgravity. Some of these devices will also separate proteins by zone electrophoresis, isotachophoresis, or isoelectric focusing in a single unit. Separation experiments with standard test particles are useful and necessary for testing and optimizing new space hardware. A cohesive free fluid electrophoresis program in the future will obviously require (1) flight opportunities and funding, (2) identification of suitable cellular and macromolecular candidate samples, and (3) provision of a proper interface of electrophoresis processing equipment with biotechnological facilities--equipment like bioreactors and protein crystal growth chambers. The authors feel that such capabilities will lead to the production of commercially useful quantities of target products and to an accumulation of new knowledge relating to the complexities of electrostatic phenomena at the cell surface.

Cellular electrophoretic mobility data: a first approach to a database.

Cellular electrophoretic mobility values of 288 types of eucaryotic cells were collected from literature published worldwide by a series of authors during the past forty years and arranged in a list. This list contains well-known recent electrophoretic results and also data that cannot be found anymore with modern literature retrieval systems. It will be a valuable help for scientists trying to purify cell populations. In addition, it confirms the observation that most eucaryotic cells have very similar electrophoretic mobilities, ranging from 40% above to 50% below the electrophoretic mobility of human erythrocytes, and thus reinforces the suggestion that electrophoretic mobilities of eucaryotic cells are subjected to strong biological controls.

Cellular changes in microgravity and the design of space radiation experiments.

Cell metabolism, secretion and cell-cell interactions can be altered during space flight. Early radiobiology experiments have demonstrated synergistic effects of radiation and microgravity as indicated by increased mutagenesis, increased chromosome aberrations, inhibited development, and retarded growth. Microgravity-induced changes in immune cell functions include reduced blastogenesis and cell-mediated, delayed-type hypersensitivity responses, increased cytokine secretions, but inhibited cytotoxic effects and macrophage differentiation. These effects are important because of the high radiosensitivity of immune cells. It is difficult to compare ground studies with space radiation biology experiments because of the complexity of the space radiation environment, types of radiation damage and repair mechanisms. Altered intracellular functions and molecular mechanisms must be considered in the design and interpretation of space radiation experiments. Critical steps in radiocarcinogenesis could be affected. New cell systems and hardware are needed to determine the biological effectiveness of the low dose rate, isotropic, multispectral space radiation and the potential usefulness of radioprotectants during space flight.

Production and action of cytokines in space.

B6MP102 cells, a continuously cultured murine bone marrow macrophage cell line, were tested for secretion of tumor necrosis factor-alpha and Interleukin-1 during space flight. We found that B6MP102 cells secreted more tumor necrosis factor-alpha and interleukin-1 when stimulated in space with lipopolysaccharide than controls similarly stimulated on earth. This compared to increased secretion of interferon-beta and -gamma by lymphocytes that was measured on the same shuttle flights. Although space flight enhanced B6MP102 secretion of tumor necrosis factor-alpha, an experiment on a subsequent space flight (STS-50) found that cellular cytotoxicity, mediated by tumor necrosis factor-alpha, was inhibited.

Age at first childbirth and later poverty.

PIP: A linear structural equation model is used in this research study in order to estimate the simultaneous effects of age at first birth on a woman's subsequent socioeconomic conditions and related outcomes after the age of 27 years. Estimation was accomplished with a variant of Amemiya's principle and a feasible generalized least squares estimator. Analysis involved examination of the bivariate relationship between age at first birth and poverty at age 27 years for Blacks, Hispanics, and Whites, followed by structural equation models for each racial group and then analysis of the total and indirect effects of age at first birth on poverty. Poverty is measured as the ratio of family income to the poverty threshold. Findings indicate that the association between early childbearing and poverty at the age of 27 years is very strong. Young women with educated parents and women with reading materials in their home before the age of 14 years achieved more schooling. When these effects were controlled, being raised by both parents and having more siblings were only associated with more schooling among Whites. Rural Blacks and Whites completed more schooling than rural Hispanics. Blacks in poor states had lower educational attainment. Age at first birth was only significant among Hispanics. First birth was delayed by 1.26 years among Blacks, 0.88 years among Whites, and 0.98 years among Hispanics for having an additional year of schooling. Delaying marriage had the strongest effect among Whites. Delayed childbearing among Blacks was predicted by having fewer siblings, being raised by both parents, and later menstruation. Earlier White childbearing was associated with women from larger families and women with larger ideal family sizes. Hispanic women raised by both parents was associated with delayed childbearing. Findings confirm that age at first birth was associated for all racial groups with poverty. Age at first birth affected educational attainment of Hispanics and age at first marriage among Whites. Age at first birth impacted on poverty through the number of children among Blacks and Whites, White and Hispanic women's earnings, and Hispanic earnings among other household members. Delaying first births had minimal impact on later poverty among Blacks and considerable impact among Whites and Hispanics.^ieng

Consequences of teen-age parenting.

The changing context of teen-age childbearing and current related controversies are reviewed. Recent research about the consequences of teen-age childbearing for the teen-age mother, the father, and for the children born is examined. The article also summarizes current knowledge about the consequences of teen-age childbearing with regard to the mother's educational attainment, marital experience, subsequent fertility behavior, labor force experience and occupational attainment, and experience with poverty and welfare.

Cytokine secretion by immune cells in space.

Cultured, bone marrow-derived macrophages, murine spleen and lymph node cells, and human lymphocytes were tested for their ability to secrete cytokines in space. Lipopolysaccharide-activated bone marrow macrophages were found to secrete significantly more interleukin-1 and tumor necrosis factor when stimulated in space than when stimulated on earth. Murine spleen cells stimulated with poly I:C in space released significantly more interferon-alpha at 1 and 14 hours after stimulation than cells stimulated on earth. Similarly, murine lymph node T cells and human peripheral blood lymphocytes, stimulated with concanavalin A in space, secreted significantly more interferon-gamma than ground controls. These data suggest that space flight has a significant enhancing effect on immune cell release of cytokines in vitro.

Experiments with suspended cells on the Space Shuttle.

Spaceflight experiments since 1981 have demonstrated that certain cell functions are altered by micro-g. Biophysical models suggest that cell membranes and organelles should not be affected directly by gravity, however, the chemical microenvironment surrounding the cell and molecular transport could be altered by reduced gravity. Most experiments have used suspended live cells in small chambers without stirring or medium exchange. Flight results include increased attachment of anchorage-dependent human cells to collagen coated microcarriers, reduced secretion of growth hormone from pituitary cells, decreased mitogenic response of lymphocytes, increased Interferon-alpha by lymphocytes, increased Interleukin-1 and Tumor Necrosis Factor secretion by macrophages. Related experiments on cells immediately postflight and on procaryotic cells have shown significant changes in secretory capacity, cell proliferation, differentiation and development. Postulated mechanism include altered cell-cell interactions, altered calcium ion transport, effects on cell cytoskeleton, transport of transmitters and interactions with receptors. The discussion includes use of new molecular methods, considerations for cell environmental control and a preview of several experiments planned for the Shuttle and Spacelab flights to study the basic effects of microgravity on cellular physiology and potential interactions of spaceflight with radiation damage and cellular repair mechanisms.

Further analyses of human kidney cell populations separated on the Space Shuttle.

Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120 degrees C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantitation of plasminogen activators in these samples. These assays of frozen culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator producing cells from non-producing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one another.

Longitudinal studies of effects of divorce on children in Great Britain and the United States.

National, longitudinal surveys from Great Britain and the United States were used to investigate the effects of divorce on children. In both studies, a subsample of children who were in two-parent families during the initial interview (at age 7 in the British data and at ages 7 to 11 in the U.S. data) were followed through the next interview (at age 11 and ages 11 to 16, respectively). At both time points in the British data, parents and teachers independently rated the children's behavior problems, and the children were given reading and mathematics achievement tests. At both time points in the U.S. data, parents rated the children's behavior problems. Children whose parents divorced or separated between the two time points were compared to children whose families remained intact. For boys, the apparent effect of separation or divorce on behavior problems and achievement at the later time point was sharply reduced by considering behavior problems, achievement levels, and family difficulties that were present at the earlier time point, before any of the families had broken up. For girls, the reduction in the apparent effect of divorce occurred to a lesser but still noticeable extent once preexisting conditions were considered.

Parallel line analysis: multifunctional software for the biomedical sciences.

An easy to use, interactive FORTRAN program for analyzing the results of parallel line assays is described. The program is menu driven and consists of five major components: data entry, data editing, manual analysis, manual plotting, and automatic analysis and plotting. Data can be entered from the terminal or from previously created data files. The data editing portion of the program is used to inspect and modify data and to statistically identify outliers. The manual analysis component is used to test the assumptions necessary for parallel line assays using analysis of covariance techniques and to determine potency ratios with confidence limits. The manual plotting component provides a graphic display of the data on the terminal screen or on a standard line printer. The automatic portion runs through multiple analyses without operator input. Data may be saved in a special file to expedite input at a future time.

The antecedents of teenage fatherhood.

The High School and Beyond Survey was used to describe young men who are at risk of becoming teenage fathers and examine the causal process leading to early fathering for young men. Bivariate results show that men who are at risk of fathering children at a young age have unique attitudes and family, school, and dating experiences. Multivariate analyses suggest that the most cogent factors affecting teenage fathering include being black, going steady, and having unorthodox views about parenting outside of marriage.