The role of growth factors and related agents in accelerating fracture healing.
Explore the source record for details and available documents.
Bone Morphogenetic Protein 2↗
Biomedical subjects
L Mills
Publications and source records attributed to L Mills.
Positive, site-specific associations between bone mineral status, fitness, and time spent at high-impact activities in 16- to 18-year-old boys.
The incidence of hip and forearm fracture in elderly men in the United Kingdom is a public health issue, but there is limited knowledge on lifestyle factors affecting male bone health. The aim of this cross-sectional study was to evaluate the relationships between whole body and regional bone mineral status and self-reported participation time in no-, low-, moderate-, and high-impact activities and fitness measurements in 16- to 18-year-old boys. One hundred twenty-eight boys underwent absorptiometry (DXA) measurements (Hologic QDR 1000W) of bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the whole body, hip, spine, and forearm. They also completed the EPIC (European Prospective Investigation of Cancer) physical activity questionnaire, which allowed categorization of activities according to impact and aerobic intensity. Fitness and strength were assessed in each subject using estimated VO2 max, grip strength, and back strength. Significant positive relationships were found between BMC, BA, and BMD and the fitness and strength measurements and participation time in high-impact sports at most skeletal sites. The relationships were further examined after adjustment of BMC for height, weight, and bone area, thereby minimizing the influence of body and bone size on these relationships. VO2 max was a significant positive determinant of size-adjusted BMC at the whole body, the ultradistal and one-third radius, and all the hip sites, except the trochanter. Size-adjusted BMC at the forearm sites and trochanter was significantly positively associated with grip strength. Size-adjusted BMC at the whole body and all the hip sites was significantly positively associated with time spent at high-impact activities. Differences in size-adjusted BMC across thirds of time spent at high-impact activities were also examined. Boys in the highest third of high-impact activity had significantly greater size-adjusted whole body BMC and total hip BMC compared to subjects in the lowest third [+3.4 (1.2)% for whole body and +8.5 (2.2)% for hip, both P = 0.001]. Boys in the highest third of high-impact activity spent most activity time jogging, playing tennis, football and rugby, basketball, and exercising with weights. Back strength and lean mass were significantly greater in subjects in the highest third compared to those in the middle (P = 0.02) and lowest third (P = 0.03). No significant differences were found between subjects in each third of high-impact activity for potential confounders including TV viewing, calcium intake, body fat, and height. These findings indicate that participation of male adolescents in a range of high-impact activities for 1 h or more a day is associated with greater bone size and mineral content, especially at the hip.
Adolescent↗
An MMP-2/MMP-9 inhibitor, 5a, enhances apoptosis induced by ligands of the TNF receptor superfamily in cancer cells.
Several studies have shown that matrix metalloproteases (MMPs) promote tumor growth, invasion, and metastasis. Consequently, MMP inhibitors have been developed as a new class of anticancer drugs, many of which are in clinical trials. The exact mechanism of the antineoplastic activity of MMP antagonists is unknown. To investigate the mechanism, we hypothesized that MMP inhibitors enhance the actions of apoptosis-inducing agents. To test this hypothesis, we treated breast, melanoma, leukemia, osteosarcoma, and normal breast epithelial cells with (2R)-2-[(4-biphenylsulfonyl)amino]-3-phenylproprionic acid (compound 5a), an organic inhibitor of MMP-2/MMP-9, alone or in combination with TNFalpha or other apoptotic agents. FACS analysis showed that 5a interacted synergistically with ligands of the TNF receptor superfamily, including TNFalpha and TNF receptor-like apoptosis-inducing ligand (TRAIL), and with a Fas-cross-linking antibody (CH11), UV, paclitaxel, thapsigargin, and staurosporin, to induce apoptosis in a cell-type-specific manner. Other MMP inhibitors did not synergize with TNFalpha. Compound 5a did not act directly on the mitochondrion or via changes in protein synthesis. Instead, the mechanism requires ligand-receptor interaction and caspase 8 activation. Investigation of the effect of 5a on tumor growth in vivo revealed that continuous treatment of subcutaneous melanoma with a combination of 5a plus TRAIL reduced tumor growth and angiogenesis in nude mice. Our data demonstrate that 5a possesses a novel proapoptotic function, thus providing an alternative mechanism for its antineoplastic action. These observations have important implications for combination cancer therapy.
Animals↗
Effect of 17beta-estradiol, o,p'-DDT, octylphenol and p,p'-DDE on gonadal development and liver and kidney pathology in juvenile male summer flounder (Paralichthys dentatus).
The intent of this study was to compare histopathologically the effect of 17beta-estradiol (E(2)), o,p'-DDT, octylphenol and p,p'-DDE on gonadal development and liver and kidney condition in sexually immature (juvenile) summer flounder (Paralichthys dentatus). The dorsal sinus of 2-year-old juvenile male summer flounder was injected with the appropriate amount of chemical incorporated in coconut oil. A second identical injection was administered 2 weeks later. Fish were sampled at 4, 6 and 8 weeks after the initial injection and observed histopathologically. In control fish, spermatogenesis was predominantly in mid to late maturation. In fish treated with 1.0 and 10.0 mg/kg E(2) spermatogenesis regressed to primary spermatogonia or an immature functional state. Testicular atrophy and spermatogonial proliferation was also observed. An eosin-positive, hyaline material was found in the gonad, liver and kidney. This eosinophilic material also stained positive with Periodic Acid Schiff (PAS) stain. Treatment of 30 or 60 mg/kg o,p'-DDT elicited altered gonadal development similar to that observed with E(2) treated fish. Octylphenol treatment of 100 mg/kg resulted in reduced testicular size, ducts full of sperm, numerous spermatogonia and PAS positive material in the testis with no developing sperm cysts. No effect on liver or gonad tissues was observed with p,p'-DDE at the concentrations tested. All chemicals tested, with exception of p,p'-DDE, altered gonadal development, whereas only E(2) caused histopathological changes in the liver and kidney. Estrogenic activity induced the liver to produce a vitellogenin (VtG)-like substance and inhibited testicular maturation. As a result, both the lack of target cells for VtG and a continuous supply of VtG from the liver allowed the hyaline material to accumulate in the liver, testis and kidney causing histopathological changes.
Animals↗
A preliminary examination of adolescent girls' perceptions of the parental knowledge of their boyfriends.
STUDY OBJECTIVE: The purpose of this study was to describe adolescent girls' perceptions of their parents' contact with and knowledge of the girls' boyfriends. A second objective was to determine if knowledge was related to demographic characteristics of the girls or aspects of the relationship with their boyfriend. DESIGN: Cross-sectional analysis of data from an interview with adolescent girls enrolled in a longitudinal study. SETTING: Urban adolescent medicine clinic. PARTICIPANTS: Adolescent girls (n = 109) with a mean age of 17.6 (range 14.9-19.3 yr). Eighty percent were African-American and 20% were Caucasian. RESULTS: Most girls reported that their parents had some contact (either in person or on the phone) with their boyfriends. Thirteen girls reported that their parents did not know their boyfriends well, 40 reported that their parents knew their boyfriends somewhat, and 56 reported that their parents knew their boyfriends well. Age, race, and sexual experience were not related to how well the parents knew the boyfriend. Girls who had been involved with their boyfriends longer, believed that their relationship would last longer, were more satisfied, were more likely to tell their boyfriends private information and were more likely to describe their parents as knowing their boyfriends well. CONCLUSIONS: These results provide an initial description of girls' perceptions of their parents' relationships with their boyfriends. It would be important to understand how to utilize the information regarding these parental-boyfriend relationships to further adolescent girls' development of healthy (both psychologically and physically) relationships.
Adolescent↗
Sexual initiation: predictors and developmental trends.
BACKGROUND: Early initiation of sexual intercourse is associated with increased risk for acquiring sexually transmitted diseases. GOAL: To examine variables related to sexual initiation and developmental changes in the reasons why adolescent girls have sexual intercourse. STUDY DESIGN: A longitudinal study of girls recruited from an adolescent medicine clinic was performed. RESULTS: Logistic regression showed that girls who described their families as being expressive, having a moral-religious emphasis, providing supervision, and having greater maternal education, and who experienced menarche at an older age were older at sexual initiation. On the basis of contingency analyses, younger girls were less likely to report attraction or love, and more likely to report peers having sex as a reason for sexual intercourse at initiation. A generalized estimating equation analysis indicated that girls at younger ages are more likely to report curiosity, a grown-up feeling, partner pressure, and friends having sexual intercourse as reasons for intercourse. Girls at older ages are more likely to report a feeling of being in love, physical attraction, too excited to stop, drunk or high partner, and feeling romantic as reasons for having sexual intercourse. CONCLUSIONS: Prevention programs should include a focus on familial characteristics and susceptibility to peer norms. They should be conducted with sensitivity to the developmental changes in intimate relationships that occur during adolescence.
Adolescent↗
Comparison of sampling methods for obtaining accurate coagulation values in hemodialysis patients with heparinized central venous catheters.
Monitoring coagulation values in hemodialysis (HD) is integral to the care of patients with central venous catheters (CVCs) to maintain catheter patency. HD patients can have problems providing blood samples and may experience discomfort with venipuncture, but no consensus in the literature is available to identify a reliable and efficient method of obtaining an international normalization ratio (INR) value from a heparinized CVC line. This was a comparative study of three different methods of blood sampling for INR values. The INR samples were obtained from a peripheral venipuncture site, the CVC line, and the arterial bloodline sample port. The peripheral INR sample was used as the gold standard. The study occurred in a 60-station hemodialysis center in a 428-bed, urban, acute care hospital. The sample included 33 HD patients with patent dialysis CVC lines. Blood samples were drawn with a standardized protocol during one HD session from each of the three sites. The Pearson correlation coefficient for the peripheral sample versus the CVC line sample was 0.97 (p < 0.001) and was 0.99 (p < 0.001) between the peripheral sample and the arterial bloodline sample. Results revealed that both alternative methods are suitable for taking INR samples. As a result of this study, the arterial bloodline sample port method for INR sampling was introduced into the HD unit at this hospital. This method has proven to be simple, quick, accurate, and noninvasive to renal patients.
Adolescent↗
Use of pulse field gel electrophoresis for the epidemiological characterisation of coagulase positive Staphylococcus isolated from meat workers and beef carcasses.
Coagulase positive staphylococci isolated at an Australian abattoir, from beef carcasses, hands, and environmental samples, were typed by the DNA macrorestriction patterns obtained following PFGE of SmaI digests. The predominant PFGE pattern of isolates collected before evisceration was different from the dominant pattern of isolates collected after evisceration. PFGE patterns for isolates from workers' hands and from concordant carcasses were indistinguishable. PFGE types among isolates collected from non-evisceration abattoir personnel and clerical staff were distinct from patterns among isolates collected from the slaughter floor personnel. Twenty-nine (85%) of the 34 isolates collected from carcasses after evisceration exhibited PFGE patterns that were 93% homologous. During evisceration the carcasses were handled extensively and it is proposed that the hands of workers at this abattoir are the primary source of staphylococcal contamination of carcasses on the slaughter floor. This paper highlights the usefulness of PFGE as an epidemiological tool for determining the source of staphylococcal contamination in the food industry.
Abattoirs↗
Incidence of coagulase positive Staphylococcus on beef carcasses in three Australian abattoirs.
The contamination of beef carcasses with coagulase-positive staphylococci (CPS) was studied at three beef abattoirs (A, B and C). The incidence and the number of CPS were determined on cattle hides immediately after slaughter and on three carcass sites (brisket, flank and round) at different points during processing along the slaughter line. The incidence of CPS on cattle hides ranged from 20 to 68.6%. At abattoir A, 6.5% of the carcasses sampled before evisceration were contaminated with CPS, compared to 40% of the carcasses after evisceration. The incidence on carcasses changed little during further processing; however, after chilling for 72 h, the incidence increased to 83%. After evisceration, the brisket and flank areas were more often contaminated than the round. A similar pattern of contamination was observed at abattoir B. At abattoir C, 26.7% of the samples collected before evisceration were contaminated and this fell to 16.7% after evisceration. After chilling for 72 h, the incidence of carcass contamination with CPS increased to 46.7%. The average number of CPS on contaminated carcasses prior to and after overnight chilling was less than 50 colony-forming units (cfu)/cm2 and, after weekend chilling, increased to 64 and 112 cfu/cm2 in abattoirs A and B, respectively. Of the isolates tested, 71.4% produced staphylococcal enterotoxin and 21% could not be classified phenotypically. The hands of workers and environmental sites associated with the evisceration process were examined for CPS at abattoir A. Hands were heavily contaminated and were the likely source of CPS contamination at this abattoir.
Abattoirs↗
Massage therapy for patients undergoing autologous bone marrow transplantation.
The purpose of the current study was to examine the impact of massage therapy on psychological, physical, and psychophysiological measures in patients undergoing autologous bone marrow transplantation (BMT). Patients scheduled to undergo BMT were randomly assigned to receive either (a) massage therapy, consisting of 20-minute sessions of shoulder, neck, head, and facial massage, or (b) standard treatment. Overall effects of massage therapy on anxiety, depression, and mood were assessed pretreatment, midtreatment, and prior to discharge using the State-Trait Anxiety Inventory, Beck Depression Inventory, and Brief Profile of Mood States, respectively. The immediate effects of massage were measured via the State Anxiety Inventory, Numerical Scales of Distress, Fatigue, Nausea, and Pain and indices of psychophysiological arousal (heart rate, blood pressure, and respiration rate), collected prior to and following patients' first, fifth, and final massage (on Days--7, midtreatment, and predischarge). Analysis of the data evaluating the immediate effects of massage showed that patients in the massage therapy group demonstrated significantly larger reductions in distress, fatigue, nausea, and State Anxiety than the standard treatment group at Day-7, in State Anxiety at midtreatment, and in fatigue at the predischarge assessment. The overall measures of psychological symptoms measured at pretreatment, midtreatment, and prior to discharge showed no overall group differences, although the massage group scored significantly lower on the State Anxiety Inventory than the standard care group at the midtreatment assessment. The two groups together showed significant declines through time on scores from the Profile of Mood States and State and Trait Anxiety Inventories.
Adult↗
Antibiotic use for the treatment of upper respiratory infections in a diverse community.
BACKGROUND: Previous studies have not addressed whether cultural factors influence beliefs and practices related to the treatment of upper respiratory infections (URIs). The purpose of our project was to assess beliefs, care-seeking behavior, use of antibiotics, and means of obtaining antibiotics for the treatment of URIs among different ethnic groups in an urban community. METHODS: A total of 192 adults completed a self-administered questionnaire indicating their likelihood of seeking care, the perceived effectiveness of treatment methods, and their usual use of treatment regimens for 2 scenarios consistent with uncomplicated URIs. Respondents were also asked about their use of antibiotics not prescribed by a physician for a URI. RESULTS: A majority of subjects reported a belief in the effectiveness of antibiotics for URIs and indicated they are likely to seek care for URIs. Many (26%) had obtained antibiotics from sources other than a physician's prescription (e.g., directly from pharmacists or a supplier outside the United States). Many (31%) believed that antibiotics should be available over the counter. Individuals who reported using antibiotics for a URI were more likely than those who did not to obtain them without a prescription (35% vs. 11%, P = .001). Subjects with a cultural background from countries where antibiotics are available over the counter are more likely to use antibiotics not prescribed by a physician than those from countries with variably enforced regulations or the United States (40%, 30%, and 20%, respectively, P = .049). CONCLUSIONS: Members of an ethnically diverse community believe antibiotics are effective for colds, are very likely to seek care for colds, and often obtain antibiotics without a prescription. The ease of antibiotic access worldwide may influence their use in some communities in the United States.
Adult↗
Effect of nitric oxide on hemoprotein-catalyzed oxidative reactions.
Hemoglobin or myoglobin-catalyzed oxidation reactions have been suggested to initiate and/or exacerbate tissue injury associated with a variety of pathological conditions including post-ischemic tissue injury, hemorrhagic disorders, and chronic inflammation. In the present study, we investigated what effect different fluxes of nitric oxide (NO) have on hemoprotein-catalyzed oxidation reactions in vitro. The hypoxanthine/xanthine oxidase system was used to generate both O2- and H2O2, whereas the spontaneous decomposition of the spermine/NO adduct was used to generate NO at a known and constant rate. We assessed the ability of myoglobin (Mb) or hemoglobin (Hb) to oxidize dihydrorhodamine (DHR) to rhodamine (RH) in the presence of O2-/H2O2 and/or NO. In the presence of a constant flux of O2- and H2O2 (1 nmol/min each), 500 nM MetMb (Fe3+) stimulated DHR oxidation from normally undetectable levels to approximately 35 microM. This oxidation reaction was inhibited by catalase but not SOD, suggesting the formation of the ferryl-hemoprotein adduct (Fe4+). Equimolar fluxes of O2-, H2O2, and NO increased further DHR oxidation to approximately 50 microM. The 15 microM increase in DHR oxidation was independent of heme concentration and was inhibited by SOD. This suggested that equal fluxes of O2- and NO interact to yield a potent oxidant such as peroxinitrite (OONO-) which together with Mb-Fe4+ oxidizes DHR. Further increases in NO fluxes significantly inhibited DHR oxidation (80%) via the NO-dependent inhibition of Mb-Fe4+ formation. Additional studies using methemoglobin (Hb-Fe3+)-catalyzed oxidative reactions yielded virtually identical results. We conclude that in the presence of a hemoprotein such as myoglobin or hemoglobin, NO may promote or inhibit oxidation reactions depending upon the relative fluxes of O2-, H2O2, and NO.
Catalase↗
A PCR specific for Escherichia coli O157 based on the rfb locus encoding O157 lipopolysaccharide.
A PCR was developed for the detection of Escherichia coli O157 based on the rfbE O-antigen synthesis genes. A 479-bp PCR product was amplified specifically from E. coli O157 in cell lysates containing 200 or 2 CFU following crude DNA extraction. The PCR detected < 1 CFU of E. coli O157 per ml in raw milk following enrichment.
Animals↗
Smith-Lemli-Opitz syndrome: a variable clinical and biochemical phenotype.
We have reviewed all known UK cases of Smith-Lemli-Opitz syndrome. Among 49 cases with proven 7-dehydrocholesterol reductase deficiency, half had been terminated or had died in infancy. The minimum incidence is 1 in 60,000. The frequent occurrence of hypospadias may account for 71% of recognised cases being male. Important common features which emerged include short thumbs, severe photosensitivity, aggressive behaviour, and atrioventricular septal defect. The typical facial appearance becomes less obvious with age and 20% of cases did not have 2/3 toe syndactyly. Biochemical measurements of serum 7-dehydrocholesterol did not correlate with clinical severity.
Adult↗
Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant.
PURPOSE: To determine the incidence of myelodysplasia (MDS) and/or acute leukemia (AL) in breast cancer patients after high-dose chemotherapy (HDC) with a single conditioning regimen and autologous bone marrow transplant (ABMT), and analyze the cytogenetic abnormalities that arise after HDC. PATIENTS AND METHODS: We retrospectively reviewed the records of 864 breast cancer patients who underwent ABMT at Duke University Medical Center, Durham, NC, from 1985 through 1996 who received the same preparative regimen of cyclophosphamide 1,875 mg/m2 for 3 days, cisplatin 55 mg/m2 for 3 days, and BCNU 600 mg/m2 for 1 day (CPB). Pretransplant cytogenetics were analyzed in all patients and posttransplant cytogenetics were evaluated in four of five patients who developed MDS/AL. RESULTS: Five of 864 patients developed MDS/AL after HDC with CPB and ABMT. The crude cumulative incidence of MDS/AL was 0.58%. The Kaplan-Meier curve shows a 4-year probability of developing MDS/AL of 1.6%. Pretransplant cytogenetics performed on these five patients were all normal. Posttransplant cytogenetics were performed on four of five patients and they were abnormal in all four, although only one patient had the most common cytogenetic abnormality associated with secondary MDS/AL (chromosome 5 and/or 7 abnormality). CONCLUSION: Whereas MDS/AL is a potential complication of HDC with CPB and ABMT, the incidence in this series of patients with breast cancer was relatively low compared with that reported in patients with non-Hodgkin's lymphoma who underwent ABMT. The cytogenetic abnormalities reported in this group of breast cancer patients were not typical of those seen in prior reports of secondary MDS/AL and appear to have occurred after HDC.
Acute Disease↗
It's a jungle out there. Some managers have learned how to hack through regulatory red tape.
Explore the source record for details and available documents.
Building Codes↗
Mix and meld design blends patients, promotes healing.
Explore the source record for details and available documents.
Ambulatory Care Facilities↗
Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.
Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.
Adult↗