Injuries from interpersonal violence presenting to a rural health center in Western Kenya: characteristics and correlates.

OBJECTIVE: To define the scope of injury due to interpersonal violence in a medium-sized town in Western Kenya. DESIGN: Prospective, cross-sectional data collection and analysis. SETTING/SUBJECTS: Data were prospectively collected on all injured patients (n = 562) presenting to a health center in Western Kenya, 2002-2004. Age, gender, type, and severity of injury, relationship to assailant, disposition, and clinician's suspicion of alcohol use were recorded. MAIN OUTCOME MEASURES: Number of injuries due to interpersonal violence; correlation of gender, alcohol use, relationship to assailant, and type of injury. RESULTS: Interpersonal violence caused 43% of all injuries. Men and women were equally likely to suffer violent injuries (42% vs 45%); however, women were more likely to suffer injury from domestic violence (4.7% vs 7.0%) and sexual assault (0% vs 3.5%). Men and women were equally likely to know their assailant. Women were more likely to be injured by a spouse/partner (19% vs 1.3%), whereas men were more likely to be injured by an acquaintance (29% vs 16%). Alcohol use was more often suspected for victims of violent, as opposed to unintentional, injury (45% vs 16%). Men with violent injuries were more likely than women to be suspected of having used alcohol (51% vs 35%). CONCLUSIONS: Interpersonal violence is a leading cause of injury in Western Kenya. Although men and women are equally likely to be assaulted, women are more likely to be injured by a spouse, and men by an acquaintance. Alcohol use is common among those who suffer violent injuries in this population.

Assessment of the relationship of demographic and social factors with intimate partner violence (IPV) among Latinas in Indianapolis.

AIMS: Indianapolis has a rapidly growing Latino community. Through our educational outreach activities in this community during the last several years, we have identified intimate partner violence (IPV) as a significant issue, as it is in all groups in the United States. Thus, we examined the prevalence of and demographic factors and behaviors associated with IPV. METHODS: We conducted an exploratory, cross-sectional study of 100 Latinas attending community health centers, educational presentations, and health fairs. Two questionnaires, one mainly demographic and one assessing IPV, were administered in Spanish or English. We used univariate and multivariate logistic regression to examine the relationships of the variables with IPV. RESULTS: The majority (75.5%) of respondents were immigrants from Mexico. Only four were born in the United States. Fifty-one percent of all respondents had experienced some form of IPV. Univariate models found drinking, marital status, and presence of parent(s) in household all significant at the alpha = 0.15 level. Multivariate models indicated that only alcohol consumption by a woman or her partner was significantly associated with IPV (p = 0.0065). CONCLUSIONS: In this exploratory study, alcohol consumption was statistically significantly associated with IPV. The use of tailored strategies to reduce alcohol use may be warranted in populations with high IPV prevalence. Future studies should examine the utility of such interventions.

Effects of a selective cyclooxygenase-2 inhibitor on cancer cells in vitro.

The cyclooxygenase (COX) family of enzymes has been implicated in cell proliferation and angiogenesis in many tumors, including colon cancer. Indeed, cyclooxygenase-2 (COX-2) inhibitors recently have been approved for use for prophylaxis in individuals with familial adenomatous polyposis. We now report on the effects of a selective COX-2 inhibitor, celecoxib, on cell proliferation, matrix metalloproteinase (MMP) concentration, angiogenesis using an in vitro assay, and apoptosis in several human cancer cell lines. We demonstrate that celecoxib modestly reduces proliferation in some cell lines and does not affect MMP concentrations. However, celecoxib significantly decreases microtubule formation in stimulated human umbilical vein endothelial cells (HUVECs) exposed to cancer cell supernatants, an in vitro angiogenesis model, when compared to controls incubated with supernatants from untreated cells. Celecoxib does not consistently induce apoptosis in these cell lines, as determined by DNA laddering in agarose gels and by a caspase assay. Thus, it appears that COX-2 inhibitors have beneficial effects in reducing malignant cell behavior in vitro and warrant further study to elucidate their mechanisms of action and to examine their mechanisms of action in this role and their utility in vivo in a variety of animal and human tumors.

Test for measuring the stretchability of melted cheese.

A test for measuring the stretchability of cheese was developed by adapting a texture-profile analyzer to pull strands of cheese upwards from a reservoir of melted cheese. Seven different cheeses were analyzed using the Utah State University stretch test. The cheeses were also analyzed for apparent viscosity with a helical viscometer, for meltability using a tube melt test, and for stretch using the pizza-fork test. Cheese was placed into a stainless steel cup and tempered in a water bath at 60, 70, 80, or 90 degrees C for 30 min before analysis. The cup was then placed in a water-jacketed holder mounted on the base of the instrument. A three-pronged hook-shaped probe was lowered into the melted cheese and then pulled vertically until all cheese strands broke or 30 cm was reached. This produced a stretch profile as the probe was lifted through the reservoir of melted cheese and then pulled strands of cheese upwards. Three parameters were defined to characterize the stretchability of the cheese. The maximum load, obtained as the probe was lifted through the cheese, was defined as melt strength (F(M)). The distance to which cheese strands were lifted was defined as stretch length (SL). The load exerted on the probe as the strands of cheese were being stretched was defined as stretch quality (SQ). There was a correlation between F(M) and apparent viscosity. There was also some correlation between SL measured by the fork test and SL when the cheese was tested at 90 degrees C, but no correlation occurred at lower temperatures.

Leveraging healthcare for the greater good: lessons learned from the National Centers of Excellence in Women's Health.

The creation of the National Centers of Excellence in Women's Health (CoE) program in 1996 by the Office on Women's Health, Department of Health and Human Services, included the stipulation that each institution awarded a CoE contribute at least a 25% match for the federal funds. Even the combination of these two sources of monies was insufficient for each CoE to accomplish its goals, however, so leveraging funds became necessary for each CoE to function effectively. The forms of leveraging varied from CoE to CoE, in part as a result of the institutional environment and the unique possibilities each permitted and in part as a result of the creativity of the leaders of the CoEs. This paper describes the concepts and some applications of leveraging in the setting of the CoEs, which might be applicable to other settings as well.

Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.

Development and implementation of novel community outreach methods in women's health issues: the National Centers of Excellence in Women's Health.

Numerous outreach efforts have been employed to educate both lay and professional communities about many medical issues. As part of our contracts with the Public Health Service, Office of Women's Health, Department of Health and Human Services, the National Centers of Excellence (CoEs) in Women's Health have been charged with creating innovative and effective methods of educating these audiences about the major issues involved in women's health. This mission is particularly critical in the arena of women's health, as women are responsible for approximately 75% of the healthcare decisions made by and for American families, and past efforts to provide them with good, evidence-based information have been fraught with difficulties ranging from financial to cultural. We report herein some of our successful novel outreach efforts. A common thread throughout this account is that among the most successful of the outreach activities are those that involve or incorporate existing community groups committed to women's health.

Effects of tetracyclines on angiogenesis in vitro.

Most tumors kill their hosts by the process of metastasis rather than by local growth of the primary mass. A significant factor contributing to the distant invasion of cancer cells is the ability of tumors to produce large numbers of new blood vessels in their midst, known as angiogenesis. This both provides access to nourishment for the primary cancer and enables the cells to escape from the tumor and enter the bloodstream. We have been examining agents that appear to inhibit metastasis and, in particular, angiogenesis. We now report on the ability of the synthetic tetracycline, doxycycline, and the chemically-modified tetracycline, COL-3, to inhibit angiogenesis in a quantitative in vitro assay of angiogenesis, using human umbilical vascular endothelial cells (HUVECs) attached to microcarrier beads.

Amiprilose hydrochloride for the treatment of rheumatoid arthritis.

The intent of this study was to compare, in a monotherapy framework, an optimal dose of the synthetic hexose sugar, amiprilose hydrochloride (HCl), to a placebo in the treatment of rheumatoid arthritis. In this double-blind, randomized, multi-center study, patients first underwent a washout period from disease-modifying antirheumatic drugs. Those who subsequently met flare criteria within 14 days of discontinuing previously stable doses of nonsteroidal anti-inflammatory drugs were randomized to amiprilose HCl (103 patients) or a placebo (115 patients) for the subsequent 20 weeks. Glucocorticoid or nonsteroidal anti-inflammatory drugs use was not permitted. At the baseline, demographic and disease characteristics were similar in both groups. Of patients completing the course of therapy, 73% were in the amiprilose HCl group and 66% were in the placebo group. Using an intent-to-treat analysis, numeric trends favoring amiprilose HCl treatment were found for clinical and laboratory parameters of disease activity. Compared with the placebo group, statistically significant degrees of improvement were achieved for the number of swollen joints (p /= \50% reduction in swollen joints (p

Conjugated linoleic acid content of milk and cheese from cows fed extruded oilseeds.

Extruded oilseeds were fed to 24 dairy cows to study the influence on the conjugated linoleic acid content of milk and cheese. Cows were fed one of three diets that contained forage and grain in a ratio of 47:53. A control diet containing 13.5% soybean meal was compared with diets containing 12% full fat extruded soybeans or 12% full fat extruded cottonseed. The control, extruded soybean, and extruded cottonseed diets contained 2.73, 4.89, and 4.56% fatty acids, respectively. Measurements were made during the last 5 wk of the 8-wk experiment. The DM intakes and 3.5% fat-corrected milk yields were higher for cows fed the extruded soybean and extruded cottonseed diets than for cows fed the control diet. A tendency for lower fat and protein contents in the milk of cows fed the extruded soybean and extruded cottonseed diets was detected. Most of the C18 fatty acids were increased in the milk and cheese when extruded soybeans and cottonseeds were fed. The conjugated linoleic acid content in milk and cheese increased a mean of 109% when full fat extruded soybeans were fed and increased 77% when cottonseeds were fed compared with the conjugated linoleic acid content when the control diet was fed. Processing the milk into cheese did not alter the conjugated linoleic acid content. The conjugated linoleic acid content of milk and cheese can be increased by the inclusion of full fat extruded soybeans and full fat extruded cottonseeds in the diets of dairy cows.

Effects of doxycycline on human prostate cancer cells in vitro.

Prostate cancer is the most common form of cancer in older men and the major cause of death from prostate cancer is metastatic disease. The matrix metalloproteinases (MMPs) play a significant role in the growth, invasion and metastasis of many tumors, including those of the prostate. We previously demonstrated that doxycycline, a synthetic tetracycline, inhibits MMPs and cell proliferation and induces apoptosis in several cancer cell lines. We also demonstrated that in an in vivo model of metastatic breast cancer in athymic mice doxycycline inhibits tumor size and regrowth after resection. In the present study, gelatinolytic activity in the human prostate cancer cell line, LNCaP, was suppressed and significant inhibition of cell growth occurred after exposure to 5 or 10 microg/ml of doxycycline, while cell growth was normal in untreated cells. Radioisotope incorporation into proteins was reduced by doxycycline. DNA fragmentation, consistent with apoptosis, was demonstrated in cells treated with doxycycline. These data suggest that doxycycline may have potential utility in the management of prostate cancer.

Inhibition of proliferation and induction of apoptosis by doxycycline in cultured human osteosarcoma cells.

Matrix metalloproteinases (MMPs) play a major role in the phenomena of growth, invasion, and metastasis of malignant disease. We studied the effects of doxycycline, a synthetic tetracycline that has been shown to suppress MMP activity in other solid tumors, on osteosarcoma (OSA) cell proliferation and MMP activity in vitro. OSA cells from 6 patients and from one established human tumor cell line (U2OS) (American Type Culture Collection) were cultured in the presence or absence of doxycycline. Doxycycline (10 microg/ml) suppressed OSA cell proliferation threefold to sevenfold in all cultures. MMP activity was assessed by gelatin zymography and was diminished by approximately 50% in all cultures. We examined the hypothesis that induction of apoptosis is one of the mechanisms by which doxycycline inhibits OSA cell proliferation. Ethidium bromide-stained gels of DNA from cells grown in the presence of 5 microg/ml and 10 microg/ml of doxycycline revealed laddering consistent with apoptosis after 24 hours in culture. The demonstration that doxycycline suppresses cell proliferation and MMP activity and induces apoptosis in human OSA cells in vitro suggests that this well-tolerated oral agent may be effective in the in vivo treatment of OSA.

The role of ethics committees in hospice programs.

Ethics committees are still relatively new to hospices, aside from those that are directly related to hospitals. This article takes a brief look at how one company formed and trained its ethics committees for several hospices providing care in the home setting. It delineates the composition of the committee, how the committee is trained, the functions of an operating committee, the various types of committees, and takes a look at the pitfalls and problems of such committees.

Effects of vitamin D3 on proliferation of cancer cells in vitro.

The principal cause of death from most forms of cancer is metastatic disease. Cancer cells appear to grow quickly out of the control of the normal host regulatory mechanisms. Many factors contribute to this unrestrained proliferation, including increased metalloproteinase activity causing degradation of the extracellular matrix surrounding cancer cells, angiogenesis permitting easy access of the cells to the bloodstream and decrease or loss of programmed cell death, or apoptosis, an important mechanism for removal of abnormal or senescent cells. Treatment modalities targeted towards arresting cancer cell proliferation and spread are needed to improve the survival of patients with cancer. Vitamin D3, 1,25-dihydroxychole-calciferol D3, has been shown to induce apoptosis in the human breast cancer cell line, MCF-7. We have studied the effects of three concentrations of vitamin D3 on the human breast cancer cell line, MDA-MB-435, the human prostate cancer cell line, LNCaP, and a human osteosarcoma cell line, U20S. We report here that vitamin D3 strikingly inhibits cell proliferation and induces apoptosis in all three cell lines.

Effects of functional electrical stimulation on the joints of adolescents with spinal cord injury.

Nineteen adolescent subjects with complete spinal cord injuries resulting in paraplegia or tetraplegia participated in a functional electrical stimulation (FES) program consisting of computerized, controlled exercise and/or weight bearing. The effects of stimulated exercise and standing/walking on the lower extremity joints were prospectively studied. Plain radiographs and MRIs were obtained prior to and following completion of the exercise and standing and walking stages. In addition, the joints of five subjects were studied with synovial biopsies, arthroscopy, and the analysis of serum and synovial fluid for a 550 000 dalton cartilage matrix glycoprotein (CMGP). Pre-exercise joint abnormalities secondary to the spinal cord injury improved following the stimulation program. None of the subjects developed Charcot joint changes. Upon standing with FES, one subject with poor hip coverage prior to participation developed hip subluxation which required surgical repair. No other detrimental clinical effects occurred in the lower extremity joints of subjects participating in an FES program over a 1-year period.

Effect of matrix metalloproteinase inhibitor batimastat on breast cancer regrowth and metastasis in athymic mice.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in the invasion and metastasis of human cancers by mediating the degradation of extracellular matrix components. Therefore, these enzymes constitute promising targets in the development of anticancer therapies. Batimastat ([(4-N-hydroxyamino)-2R-isobutyl-3S-(thienyl-thiomethyl)succinyl]-L- phenyl-alanine-N-methylamide) is one of a new class of agents designed to inhibit MMP activity. PURPOSE: We asked whether batimastat, given as adjuvant therapy after primary tumor resection, could inhibit local-regional tumor regrowth and the formation of lung metastases in a human breast cancer xenograft model. We also explored possible effects of batimastat on breast cancer cell viability and on the accumulation of specific messenger RNAs (mRNAs). METHODS: Human MDA-MB-435 breast cancer cells were treated in vitro for 6 days with batimastat at concentrations ranging from 0.1 to 10.0 microM, and then viable cell counts were performed. The activity of collagenases, directly associated with cultured MDA-MB-435 cells or released into their culture fluids, was assessed by gelatin zymography after 1 and 3 days of batimastat treatment (drug range, 0.2-2.0 microM). Athymic nude mice were given daily intraperitoneal injections of batimastat (30 mg/kg body weight) after resection of MDA-MB-435 primary tumors grown in their mammary fat pads; the volumes of tumor regrowths and the numbers and volumes of lung metastases were calculated; neovascularization in the regrowths was assessed by immunohistochemical analysis with an antibody directed against CD31, an endothelial cell antigen. The effect of batimastat treatment on the accumulation of mRNAs encoding specific MMPs and the tissue inhibitor of metalloproteinases-2 (TIMP-2) in cultured cells, primary tumors, and tumor regrowths was measured by RNA dot blotting and hybridization with complementary probes. Linear regression analysis, Student's t tests, and chi-squared analysis were used to evaluate the data. RESULTS: The viability of cultured MDA-MB-435 cells was not affected by treatment with batimastat; however, measured activities for the 72-kd and 92-kd collagenases released by these cells were reduced after batimastat treatment. Intraperitoneal injection of batimastat significantly inhibited the local-regional regrowth of resected MDA-MB-435 tumors in athymic nude mice (in comparison with control mice, P = .035), and it reduced the incidence (P < .05), number (P = .0001), and total volume (P = .0001) of lung metastases. Batimastat treatment did not affect cellular levels of MMP or TIMP-2 mRNAs. CONCLUSION: Batimastat inhibits human breast cancer regrowth and metastasis in a nude mouse xenograft model. Potential mechanisms for batimastat's inhibitory activity do not include direct cell toxicity or alteration of MMP or TIMP mRNA levels.

The school experience of children with arthritis. Coping in the 1990s and transition into adulthood.

To the arthritic child and his or her family, the pediatrician is a valuable resource. When school problems first occur in elementary school, the pediatrician can try to solve them with an informal contact with the school teacher, nurse, counselor, or principal. If that effort is unsuccessful, the pediatrician can then suggest that the family go to the school and request the Individual Education Plan (IEP). Although this mechanism is hardly a panacea and local school district variability exists, this process provides an opportunity for the parent and school personnel to sit down and discuss how the child's problems and illness impact school performance. Furthermore, the IEP attempts to adapt the school environment specifically for that child. The current mechanism of modification of a child's education is the result of a long, evolutionary societal and educational process. Educators now recognize that children with disabilities and chronic illnesses are entitled to an appropriate public education with a special focus on how illness can interfere with that education. Whatever congressional changes are likely in the 1990s, many of these civil rights advances for the disabled or chronically ill child should survive. The transition of the adolescent with a chronic illness, such as arthritis, into adulthood has received little attention. This is an area where a compassionate and supportive pediatrician may help prevent adolescent problems rather than simply reacting to them. A gradual, incremental transition program in the pediatric office and clinic may increase the chances that more of these special adolescents will become productive, contributing adults.