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.

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.

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

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.

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 doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells.

Metastatic disease is one of the major causes of death from cancer in human beings. Several enzyme systems have been implicated in the metastatic process, but the metalloproteinases (MPs) appear to be the major group involved in most instances of neoplastic invasion. Increased MP activity has been correlated with the metastatic potential of many cancers, including breast cancer. MPs also play a role in tumor angiogenesis. Tetracyclines are antimicrobial agents that can suppress MP activity in a variety of tissues, including gingiva, bone, and cartilage. Several reports have indicated that tetracyclines can suppress tumor MPs as well. A synthetic tetracycline, doxycycline, inhibits migration of human MDA-MB-435 breast adenocarcinoma cells through a reconstituted basement membrane (Matrigel), an assay used as an in vitro surrogate for the in vivo process of tumor invasion through basement membranes. Additionally, doxycycline diminishes the proliferation of this breast cancer cell line and also decreases its gelatinolytic activity, as determined by gel zymography.

Studies of copper transport in cultured bovine chondrocytes.

Copper serves as the cofactor for a number of important enzymes in cartilage, as well as in other tissues, including lysyl oxidase, superoxide dismutase, and cytochrome oxidase. Ceruloplasmin is responsible for the transport of approx. 95% of the copper in serum, but the mechanisms for intracellular copper transport are unknown. We have demonstrated recently that a high-molecular-weight cartilage glycoprotein, referred to as CMGP, has regions of sequence homology with ceruloplasmin. CMGP also binds copper and has at least some oxidase activity similar to that of ceruloplasmin. Other tissues synthesize intracellular ceruloplasmin-like proteins. The present report represents part of an effort to examine the hypothesis that CMGP is a copper transport protein in chondrocytes and to characterize the enzymatic activities of CMGP. These studies demonstrate that CMGP is the principal chondrocyte protein labeled by 67Cu in vitro and that the label is localized to the mitochondria, cytosol, and membrane fractions of sucrose gradients, suggesting copper transport through the cell. In parallel experiments, [3H]leucine was incorporated into proteins corresponding to the subunits and fragments of CMGP, as described previously, and in a similar distribution among the subcellular fractions as labeled copper. Additionally, CMGP has oxidase and ferroxidase activities similar to those of ceruloplasmin.

Synovial fluid and plasma levels of cartilage matrix glycoprotein in arthritis.

As cartilage matrix glycoprotein (CMGP) is a prominent matrix constituent, we analyzed the relationship of levels in plasma (CMGPP) and synovial fluid (CMGPS) to each other, to clinical diagnosis, and to degree of radiographic cartilage degeneration. CMGP was measured in matched synovial fluid and plasma specimens from 67 patients with various forms of arthritis using an ELISA technique. CMGPS consistently exceeded CMGPP, CMGPP levels correlated significantly with CMGPS levels, and CMGP retention in joint fluid, as calculated by the ratio CMGPS: CMGPP, was significantly higher in patients whose synovial fluids contain basic calcium phosphate crystals. No correlation of CMGPP or CMGPS with diagnosis or degree of cartilage degeneration was observed. CMGP measurements are not useful diagnostically in patients with chronic arthritis and do not predict degree of radiographic degeneration. The association of basic calcium phosphate crystals with intraarticular retention of CMGP warrants further study.

Evidence that a 550,000-dalton cartilage matrix glycoprotein is a chondrocyte membrane-associated protein closely related to ceruloplasmin.

Cartilage matrix glycoprotein (CMGP) is a disulfide-bonded 550,000-dalton protein that is synthesized by chondrocytes and ciliary epithelial cells. We have purified the protein from bovine and porcine articular cartilage and have sequenced two peptides, which both have significant homology with human ceruloplasmin, a copper-binding oxidase. Immunolocation analysis indicates that a commercial polyclonal antiserum to human ceruloplasmin reacts with bovine cartilage CMGP. Chelating columns made with copper bind CMGP from bovine cartilage extracts. CMGP is present in bovine chondrocyte membrane preparations purified from sucrose density gradients. Oligonucleotide probes have been synthesized based on the published sequence of the 3'-untranslated region and a portion of the C terminus of human ceruloplasmin and have been used to amplify a cDNA fragment from bovine cartilage and human liver libraries. CMGP demonstrates oxidase activity towards p-phenylenediamine similar to that of ceruloplasmin. These studies suggest that CMGP is closely related to, if not identical with, ceruloplasmin. It is possible that CMGP may be involved in metal transport into and/or within the chondrocyte.

Imaging, arthroscopy, and markers in osteoarthritis.

Osteoarthritis is the most common form of arthritis occurring in humans, but its diagnosis in early stages continues to be elusive. Early diagnosis is of great potential importance because it would allow identification of individuals at risk for progressive disease and permit early intervention. At present, perhaps even more important, the ability to recognize patients with early, often asymptomatic, disease and the ability to monitor disease progression over time would be most useful for the evaluation of new forms of therapy to prevent, halt, or even reverse osteoarthritis. Thus, 1991 has witnessed the continued search for the ideal indicator of early osteoarthritis.

Morphologic and molecular changes during the post-natal development of the rabbit vitreous.

Rabbits aged 1, 4, 10, 15, and 20 days, and 4 months were anesthetized and perfused with 4% formaldehyde. One eye of each rabbit was processed for paraffin embedding, while the other eye was embedded intact in methacrylate. Rabbits aged 1 and 15 days and 4 months were perfused with 2.5% glutaraldehyde, and the eyes were processed for Epon embedding. The paraffin sections were immunostained to allow detection of a high molecular weight cartilage matrix glycoprotein (CMGP), which is synthesized by the ciliary body and found in the vitreous in adult animals, using a specific mouse monoclonal antibody. CMGP was identified in the vitreous and in the inner layer of the ciliary epithelium only after the fifteenth day of life in amounts comparable to those detected in adult rabbits. Before this time immunostaining with the monoclonal antibody was seen only in the apical region of the inner ciliary epithelial cells. However, electron microscopic observations revealed that the cytoplasmic organelles responsible for the secretion of glycoproteins, i.e. the rough endoplasmic reticulum, Golgi apparatus, and vesicles, were present in the inner layer of ciliary epithelial cells as early as the first day of life. Anteroposterior sections of whole eyes embedded in methacrylate revealed a relatively dense meshwork of vitreous fibrils on the first day of life. The blood vessels were concentrated at the posterior region of the lens, and isolated cells were visible. The blood vessels were not seen after the age of 15 days, and the fiber meshwork and cells were inconspicuous by then.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiographic grading of the severity of knee osteoarthritis: relation of the Kellgren and Lawrence grade to a grade based on joint space narrowing, and correlation with arthroscopic evidence of articular cartilage degeneration.

We examined standing knee radiographs of 92 patients who had chronic knee pain and radiographic evidence of mild or moderate osteoarthritis (OA) according to the Kellgren and Lawrence (K/L) criteria. Because the K/L criteria overemphasize osteophytosis relative to joint space narrowing (JSN), we graded OA severity also with a scoring system that placed greater emphasis on JSN than on osteophytes. In each case, the articular cartilage was visualized directly at arthroscopy. Of 17 patients whose radiographic findings were normal by both the K/L criteria and our JSN-weighted criteria, 7 had advanced tibiofemoral and/or patellofemoral compartment changes of OA seen at arthroscopy, emphasizing the insensitivity of the radiograph for detecting early articular cartilage loss. In addition, tibiofemoral JSN was common in the presence of normal articular cartilage. The JSN-weighted scale provided no advantage over the K/L criteria for assessing the severity of articular cartilage changes of OA.

Autoradiographic, electrophoretic, and immunocytochemical studies of glycoproteins of the rabbit iris.

L-[3H]fucose was injected either intravitreally or intra-aqueously into adult rabbits which were killed at several time points after injection. SDS-polyacrylamide gel electrophoresis and fluorography of iris extracts revealed that most of the proteins are glycoproteins containing fucose residues. Autoradiography of semi-thin histologic sections demonstrated that glycoprotein synthesis was most prominent in the epithelium of the iris, while little protein synthesis was evident in the stroma of the iris. The results of these experiments indicated that the glycoproteins of the iris undergo renewal. The protein band pattern of the iris extracts was very similar to that of extracts of the ciliary body. The high-molecular-weight cartilage matrix glycoprotein (CMGP), an intrinsic component of the ciliary body, vitreous, and aqueous humor, was detected by immunohistologic studies only in the stroma of the iris. The results of immunohistochemical analyses of the eyes of young rabbits (1-21 days old), in addition to the autoradiographic findings, strongly suggest that CMGP is not an intrinsic glycoprotein of the iris stroma, at least in this species.