Building bridges to healthy skin. Treatment teams maximize healing.
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Biomedical subjects
Publications and source records attributed to C Brown.
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Although emphasis in the literature may be on the use of pressure-relieving mattresses and specialist beds, seating is also an important part of preserving tissue viability. A collaborative approach within the multidisciplinary team is of value. Equipment is of limited value if not complemented by best practice, carried out by well-educated staff. Patients' views should be elicited.
Cholesterol 7alpha-hydroxylase is the first and rate-limiting enzyme in a pathway through which cholesterol is metabolized to bile acids. The gene encoding cholesterol 7alpha-hydroxylase, CYP7A, is expressed exclusively in the liver. Overexpression of CYP7A in hamsters results in a reduction of serum cholesterol levels, suggesting that the enzyme plays a central role in cholesterol homeostasis. Here, we report the identification of a hepatic-specific transcription factor that binds to the promoter of the human CYP7A gene. We designate this factor CPF, for CYP7A promoter binding factor. Mutation of the CPF binding site within the CYP7A promoter abolished hepatic-specific expression of the gene in transient transfection assays. A cDNA encoding CPF was cloned and identified as a human homolog of the Drosophila orphan nuclear receptor fushi tarazu F1 (Ftz-F1). Cotransfection of a CPF expression plasmid and a CYP7A reporter gene resulted in specific induction of CYP7A-directed transcription. These observations suggest that CPF is a key regulator of human CYP7A gene expression in the liver.
Migration of aortic smooth muscle cells is thought to be of essential importance in vascular restenosis, remodeling, and angiogenesis. Recent studies have shown that NO donors inhibit the migration of subcultured aortic smooth muscle cells. However, there is evidence that NO elicits opposite effects on cell proliferation in primary versus subcultured cells, indicating fundamental differences among different models of aortic smooth muscle cell cultures. The purpose of the current study was to investigate the effect of NO donors on migration of primary cultures of rat aortic smooth muscle cells and to compare and contrast their response with those in subcultured cells. A second purpose was to investigate some of the underlying mechanisms associated with NO-induced effects on cell migration. We report that 2 NO donors, S-nitroso-N-acetylpenicillamine (SNAP) and 2, 2-(hydroxynitrosohydrazino)bis-ethanamine, stimulated the migration of primary cells in a wounded-culture model as well as in a transwell migration model. The effect of NO donors was mimicked by 2 cGMP analogues and C-type natriuretic peptide and blocked by a specific inhibitor of guanyl cyclase, 1H-(1,2,4)oxadiazolo[4,3, -a]quinoxalin-1-one, indicating the involvement of cGMP as second messenger. Moreover, neither NO donors nor cGMP analogues altered migration of primary cultures stimulated by either FBS or angiotensin II. In contrast to its effect in primary cultures, SNAP did not alter basal or stimulated migration of subcultured cells, except at a relatively high concentration of 1 mmol/L, at which migration was inhibited. The migration-stimulatory effect of NO donors and cGMP was associated with altered cell morphology and dissociation of actin filaments, consistent with recent studies indicating that cell morphology and cytoskeletal organization influence cell migration. The results suggest the possible involvement of NO-induced cell migration in vascular injury or remodeling, representing conditions in which vascular NO levels would be expected to be elevated.
Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) -control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.
OBJECTIVE: To retrospectively determine whether race differentially influences treatment adherence and clinical outcomes among 68 African Americans and 92 whites treated for major depression in four urban, primary care settings. METHOD: Study participants were randomly assigned to standardized interpersonal psychotherapy or pharmacotherapy with nortriptyline, and were assessed at baseline, and successive time points up to 8 months for severity of depression, and mental and physical health-related functioning. RESULTS: Intent-to-treat analyses revealed no treatment or race-specific differences in symptomatic recovery when both groups were provided standardized psychotherapy or pharmacotherapy. However, African Americans had poorer functional outcomes than whites. CONCLUSIONS: African American and white primary medical care patients are effectively treated with standardized psychotherapy and pharmacotherapy. Future research should assess the impact of cultural context on symptom presentation, psychosocial functioning, and treatment adherence and response.
Formation of uroliths is not a disease but rather a complication of several disorders. Some disorders can be identified and corrected (e.g., infection-induced struvite urolith formation), and some can be identified but not corrected (e.g., hyperuricosuria occurring in Dalmatians that form ammonium urate uroliths), although for others, the underlying etiopathogenesis is not known (e.g., calcium oxalate urolith formation in Miniature Schnauzers). A common denominator of these disorders is that from time to time, they can create oversaturation of urine with one or more crystal precursors, resulting in formation of crystals. To develop rational and effective approaches to treatment, abnormalities that promote urolith formation must be identified with the goal of eliminating or modifying them. It is therefore important to understand several basic concepts associated with urolithiasis.
Motor-related brain potentials were used to examine the time course of grammatical and phonological processes during noun phrase production in Dutch. In the experiments, participants named colored pictures using a no-determiner noun phrase. On half of the trials a syntactic-phonological classification task had to be performed before naming. Depending on the outcome of the classifications, a left or a right push-button response was given (go trials), or no push-button response was given (no-go trials). Lateralized readiness potentials (LRPs) were derived to test whether syntactic and phonological information affected the motor system at separate moments in time. The results showed that when syntactic information determined the response-hand decision, an LRP developed on no-go trials. However, no such effect was observed when phonological information determined response hand. On the basis of the data, it can be estimated that an additional period of at least 40 ms is needed to retrieve a word's initial phoneme once its lemma has been retrieved. These results provide evidence for the view that during speaking, grammatical processing precedes phonological processing in time.
The concentration of human immunodeficiency virus type 1 (HIV-1) particles in blood plasma is very predictive of the subsequent disease course in an infected individual; its measurement has become one of the most important parameters for monitoring clinical status. Steady-state virus levels in plasma reflect a balance between the rates of virions entering and leaving the peripheral blood. We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell-free particles in the presence and absence of virus-specific antibodies. Here we show, by measuring virion RNA, particle-associated p24 Gag protein and virus infectivity, that the clearance of physical and infectious particles from a primary, dual-tropic virus isolate, HIV-1DH12, is very rapid in naive animals, with half-lives ranging from 13 to 26 minutes. In the presence of high-titer HIV-1DH12-specific neutralizing antibodies, the half-life of virion RNA was considerably reduced (to 3.9-7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV-1 infectivity due to antibody binding.
The study purpose was to determine if G-CSF plus dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in superior autologous blood stem cell mobilization (BSCM) than less intensive chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non-Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14), multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially underwent BSCM by one of three methods: Group 1: G-CSF alone x 4 days (n = 30). Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions, followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group 3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21 (n = 40). A multivariate analysis was performed to determine which factors independently predicted BSCM. The median peripheral blood CD34+ (PB CD34+) cell count the morning of apheresis linearly correlated with the number of CD34+ cells removed per litre of apheresis that day. The median PB CD34+ cell count and median CD34+ cells x 10(6) removed per litre of apheresis were highest for Group 3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis, mobilization group (3 > 2 > 1), disease other than AML, no prior melphalan or mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM. Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable cancer in marrow and apheresis products after DICEP. These data suggest that DICEP results in superior BSCM than less intensive chemotherapy regimens.
Data were analyzed on 178 consecutive patients (median age 43 years) who underwent autologous blood stem cell transplantation (ABSCT) at a single institution to determine if CD34+ subsets (CD34+38-, CD34+33-, CD34+33+, CD34+41+) or various clinical factors affect hematopoietic engraftment independent of the total CD34+ cell dose/kg. Using Cox proportional hazards models, the factors independently associated with rapid neutrophil engraftment were higher CD34+ dose/kg, use of G-CSF post-ABSCT, and conditioning regimen (single-agent melphalan +/- TBI slower). Factors independently associated with rapid platelet engraftment were higher CD34+ cell dose/kg, higher ratio of CD34+33-/total CD34+ cells infused, conditioning regimen (mitoxantrone, vinblastine, cyclophosphamide faster), and no CD34+ cell selection of the autograft. The CD34+ cell selection process seemed to deplete CD34+41+ cells to a greater extent than total CD34+ cells which may explain our observation that it resulted in slower platelet engraftment. In conclusion, the total CD34+ dose/kg was a better predictor of hematopoietic engraftment following ABSCT than the dose of any CD34+ subset. Platelet engraftment, however, was also influenced by the ratio of CD34+33-/total CD34+ cells for unmanipulated autografts, and possibly by the CD34+41+ dose for autografts manipulated by CD34+ selection. The use of CD34+ subsets requires further investigation in predicting engraftment of autografts which undergo ex vivo manipulation.
We have compared the outcomes of 87 patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) receiving matched sibling transplants with stem cells from peripheral blood (blood cell transplant, BCT) or bone marrow (BMT). In good risk patients (AML in CR1) granulocytes recovered to 0.5 x 10(9)/l a median of 14 days after BCT compared with 19 days after BMT (P < 0.0001). For patients with poor risk disease (AML beyond CR1 and MDS) corresponding figures were 16 vs 26 days (P < 0.0001). Platelet recovery to 20 x 10(9)/l was also faster after BCT (good risk 12 vs 20 days, P < 0.0001; poor risk 17 vs 22 days, P = 0.04). Red cell transfusions were unaffected by cell source, but BCT recipients required less platelet transfusions (good risk 1 vs 5, P = 0.002; poor risk 5 vs 11, P = 0.004). Blood cell transplants resulted in more chronic GVHD (86% vs 48%, P = 0.005) and a significantly higher proportion of recipients with KPS of 80% or less (48% vs 5%, P = 0.004). Disease-free survival at 4 years was 23% for both groups of poor risk patients but outcome in good risk patients was better after BCT (93% vs 62%, P = 0.047) related mainly to less relapse. While disease-free survival may be better after BCT than BMT for AML in CR1, quality of life may be relatively impaired.
The purpose of this study was to compare the debonding force of orthodontic brackets bonded with two conventional resin adhesives (Resilience L3 and Light Bond) and a resin-reinforced glass ionomer cement (Fuji Ortho LC). For the in vitro part of the study, 80 extracted premolars were randomly divided into four groups. In groups A and B, brackets were bonded to unetched enamel using Fuji Ortho LC cement in wet and dry conditions, respectively. In groups C and D, brackets were bonded to etched enamel using Resilience L3 and Light Bond, respectively. Debonding force was determined using a servohydraulic testing machine at a crosshead speed of 1 mm/min. Data was analyzed using the ANOVA and Tukey-Kramer multiple comparison test at p<0.05. A significant difference was found in debonding force between unetched Fuji Ortho LC and the two conventional resins. There was no significant difference between the two conventional resins or between unetched resin-reinforced glass ionomer in the wet and dry conditions. For the in vivo part of the study, 30 patients were randomly assigned to one of the three bonding material groups. Bracket survival rates and distributions were obtained by following these patients for 1.2 years. Data was analyzed using the Kaplan-Meier product-limit estimates of survivorship function. Bond failure interface was determined using a modified adhesive remnant index (ARI). These results showed no significant difference between survival rates and distributions among the three bonding materials with respect to the type of malocclusion, type of orthodontic treatment, or location of bracket. There were significant differences between survival distributions of males and females in the unetched Fuji Ortho LC group and among type of teeth in the conventional resin groups. The predominant mode of bracket failure for the unetched Fuji Ortho LC cement was at the enamel-adhesive interface, and for conventional resins, the enamel-adhesive interface and the bracket-adhesive interface. These results suggest that resin-reinforced glass ionomer cement can withstand occlusal and orthodontic forces despite having a bond strength lower than that of conventional resin adhesives.
A questionnaire was sent to 2000 members of two of the largest national infertility support organizations as part of the National Infertility Awareness Campaign (NIAC), 1997. A total of 980 questionnaires was completed and returned to the market research company, Ballington Hall. Some 69% of the respondents were aged between 30 and 39 years. One-third of the couples had been trying for a baby for more than 3 years, including one-tenth who had been trying to conceive for more than 10 years. Some 40% of respondents were successful in conceiving, although a significant proportion of these took more than 6 years. About 75% of those surveyed had been forced to pay for some or all of their infertility treatments and investigations, whereas 18% had their treatments funded fully by the National Health Service (NHS). Funding sources for the remaining 7% were unknown. Just over one-third of respondents felt that their GP provided sufficient information about the causes of infertility investigations and treatment, while the majority said that their specialists had been helpful. One in three said that they did not fully understand the medical nature of their own or their partner's infertility. A wide range of negative emotions was experienced by respondents. One in five said they experienced suicidal feelings; one in three said that infertility had strained their relationship; and just over one-quarter found that their relationship improved as a result of the treatment. Some 71% said that they would request counselling if it were offered free, but only 12% had been provided with free counselling on the NHS.
INTRODUCTION: Nonoperative management of solid organ injury from blunt trauma in children has focused concern on potential delays in diagnosis of hollow viscus injury with resultant increases in morbidity, mortality, and cost. This study of a large pediatric trauma database will review the issues of difficulty and/or delay in diagnosis as it relates specifically to definitive treatment and outcome. METHODS: We surveyed 11,592 consecutive admissions to a designated pediatric trauma center from 1985 to 1997 to identify children with documented injury of the gastrointestinal (GI) tract from blunt trauma. The records were extensively analyzed specifically in regard to mechanism of injury, type and site of injury, time to diagnosis, operative treatment, complications, and final outcome. RESULTS: The 79 children identified, 4 months to 17 years old, included 27 females and 52 males. Mechanism of injury included 15 restrained and 7 unrestrained passengers, 15 pedestrians, 15 child abuse victims, 10 bike handlebar intrusions, 8 discrete blows to the abdomen, 4 bike versus auto, 3 falls, and 2 crush injuries. There were 51 perforations, 6 avulsions, and 22 lesser injuries including contusions. Injury of the small bowel was most common, 44 cases, followed by the duodenum, 18 cases, colon, 17 cases, and stomach, 6 cases. In 45 children, diagnosis was made quickly by a combination of obvious clinical findings, plain x-ray and/or initial computed tomographic findings mandating urgent operative intervention. Diagnosis was delayed beyond 4 hours in 34 children, beyond 24 hours in 17 children and was made by persistent clinical suspicion, aided by delayed computed tomographic findings of bowel wall edema or unexplained fluid. The six deaths were caused by severe head injury. Complications included two delayed abscesses and two cases of intestinal obstruction. All 73 survivors left the hospital with normal bowel function. CONCLUSIONS: Injury to the GI tract from blunt trauma in children is uncommon (<1%). The majority of GI tract injuries (60%) are caused by a discrete point of energy transfer such as a seatbelt (19%), a handle bar (13%), or a blow from abuse (19%), or other blows and is unique to this population. Although diagnosis may be difficult and often delayed, this did not result in excessive morbidity or mortality. Safe and effective treatment of GI tract injuries is compatible with nonoperative management of most other injuries associated with blunt abdominal trauma in children, while reducing the risk of nontherapeutic laparotomy.
Protracted conflict and violence in Burma have been conducive to the growth of the opium industry, Burma's single financial success in recent years of economic crisis and authoritarian rule. This in turn has fed violence and subsequent humanitarian crisis. This paper argues that the underlying political economy of the conflict has been overlooked, while conflict itself has been treated as a peripheral factor in questions of 'development', and further that the opium dynamic is a vital factor in continued violence and vulnerability for non-combatants in the region. A political economy approach, identifying the beneficiaries of violence, will offer a more holistic and effective approach to the protracted crisis.
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