Biomedical subjects
Publications and source records attributed to L A Robinson.
Glutamic acid derived hydroxamates were identified as potent and selective inhibitors of procollagen C-proteinase, an essential enzyme for the processing of procollagens to fibrillar collagens. Such compounds have potential therapeutic application in the treatment of fibrosis.
The parallel synthesis of novel inhibitors of procollagen C-terminal proteinase is described. The synthetic strategy allowed for the facile synthesis of a large number of side-chain diversified diamino acid hydroxamates, of which the D-diaminopropionic acid derivatives were shown to be single digit nanomolar PCP inhibitors.
OBJECTIVE: To examine the feasibility, acceptability, and effectiveness of a school based smoking cessation programme among students caught smoking at school. DESIGN: A randomised controlled trial comparing cessation rates among students in a behavioural cessation programme and those receiving self help materials only. SETTING: Eighteen schools in the Memphis, Tennessee area. SUBJECTS: Two hundred and sixty one adolescent cigarette smokers (166 male, 95 female) averaging 15.8 years of age. INTERVENTION: Students assigned to the intervention received a four session behavioural treatment programme administered individually by a health educator. In addition, these students received stage matched intervention in brief phone calls monthly until the one year follow up. MAIN OUTCOME MEASURE: Self reported and biochemically verified smoking cessation at post-test and 12 month follow up. RESULTS: Recruiting students who were caught smoking at school proved to be highly successful. Participants rated the programme favourably, and retention rates were high. Although treated participants improved more in tobacco related knowledge relative to controls (p = 0.002), there were no group differences in changes in attitudes toward smoking. In addition, treated and control participants demonstrated no significant differences in cessation rates both at post-test and follow up. Comparisons between self reported cessation rates and those obtained under bogus pipeline conditions or with biochemical verification suggested significant falsification of cessation among participants. CONCLUSIONS: Our results failed to demonstrate any significant effect of the cessation programme on smoking rates for treated adolescents compared with controls. Our findings also highlight the importance of utilising strong methodology in research on adolescent smoking cessation, including control groups and biochemical verification of smoking status.
We describe the nanofabrication study of self-aligned electrodes on suspended multiwalled carbon nanotube structures. When metal is deposited on a suspended multiwalled carbon nanotube structure, the nanotube acts as an evaporation mask, resulting in the formation of discontinuous electrodes. The metal deposits on the nanotubes are removed with lift-off. Using Al sacrificial layers, it was possible to fabricate self-aligned contact electrodes and control electrodes nanometers from the suspended carbon nanotubes with a single lithography step. It was also shown that the fabrication technique may also be used to form nano-gapped contact electrodes. The technique should prove useful for the fabrication of nano-electromechanical systems.
A discussion of the solid-phase synthesis of ornithine derived sulfonamide hydroxamic acids is illustrated. These analogues are shown to be potent, non-peptide inhibitors of procollagen C-proteinase (PCP).
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Management of the stage IIIA (N2) patient remains one of the most controversial areas in thoracic oncology. The potential curability of at least some of these patients has encouraged the development of more complex, aggressive, and toxic multimodality treatment regimens.
Radioisotope bone scanning is frequently employed in staging malignancies. However, false positive results are common, and biopsy is usually required. In the absence of plain radiographic abnormalities or local symptoms, localization of the area of abnormal tracer activity at the time of open rib or sternum biopsy may be difficult. It often requires resection of a large portion of one or more ribs or other bones to assure that the target area was biopsied, and still the area in question is commonly missed. In this setting, the newly-developed, small gamma probe is now used as a tool to allow precise intraoperative localization of increased tracer activity in the target bone. The use of gamma counting is an easy, highly accurate aid (100% sensitivity) to localize areas of abnormal radioisotope uptake in suspected asymptomatic osseous metastases, usually for open biopsy of a rib. The use of this technique obviates the need to obtain intraoperative localizing radiographs to confirm accurate rib identification, thereby substantially decreasing operative time.
The hallmark of acute allograft rejection is infiltration of the inflamed graft by circulating leukocytes. We studied the role of fractalkine (FKN) and its receptor, CX(3)CR1, in allograft rejection. FKN expression was negligible in nonrejecting cardiac isografts but was significantly enhanced in rejecting allografts. At early time points, FKN expression was particularly prominent on vascular tissues and endothelium. As rejection progressed, FKN expression was further increased, with prominent anti-FKN staining seen around vessels and on cardiac myocytes. To determine the capacity of FKN on endothelial cells to promote leukocyte adhesion, we performed adhesion assays with PBMC and monolayers of TNF-alpha-activated murine endothelial cells under low-shear conditions. Treatment with either anti-FKN or anti-CX(3)CR1-blocking Ab significantly inhibited PBMC binding, indicating that a large proportion of leukocyte binding to murine endothelium occurs via the FKN and CX(3)CR1 adhesion receptors. To determine the functional significance of FKN in rejection, we treated cardiac allograft recipients with daily injections of anti-CX(3)CR1 Ab. Treatment with the anti-CX(3)CR1 Ab significantly prolonged allograft survival from 7 +/- 1 to 49 +/- 30 days (p < 0.0008). These studies identify a critical role for FKN in the pathogenesis of acute rejection and suggest that FKN may be a useful therapeutic target in rejection.
BACKGROUND: The optimal management of an acute exacerbation of chronic heart failure (CHF) is uncertain. There is little randomized evidence available to support the various treatment strategies for patients hospitalized with an exacerbation of CHF. Inotropic agents may produce beneficial hemodynamic effects, and although they are currently used in these patients, their effect on clinical response and impact on clinical outcome is unclear. We present a unique and simple study designed to determine whether a treatment strategy for CHF exacerbations that includes an intravenous agent with inotropic properties can reduce hospital length of stay and lead to improved patient outcome. METHODS: The OPTIME CHF (Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure) trial is an ongoing multicenter, randomized, placebo-controlled trial of a treatment strategy for patients with acute exacerbations of CHF. The design of this study provides a novel approach to the evaluation of treatment strategies in the care of this population. The OPTIME CHF design uses early initiation of intravenous milrinone as both an adjunct to the best the medical therapy and to facilitate optimal dosing of standard oral therapy for heart failure. Patients with known systolic heart failure requiring hospital admission for a CHF exacerbation are randomly assigned within 48 hours of admission to receive a 48-hour infusion of either intravenous milrinone or placebo. The primary end point of this design is a reduction in the total hospital days for cardiovascular events within 60 days after therapy. Enrollment of 1000 patients began July 7, 1997, at 80 US centers and is projected to conclude in late 1999.
Early age of initiation is a significant risk factor for long-term dependent smoking and may also relate to other unhealthy behaviors. The current study assessed age of initiation in relationship to smoking dependence and motivation to quit, physical activity, dietary intake, body mass index (BMI), attitude toward illegal drug use, binge drinking, seat belt use, and smoking status at follow-up. Subjects were 7995 Air Force recruits who reported smoking regularly up to Basic Military Training. Euro-Americans initiated smoking more than a year earlier on average (15.5 years) than did African-Americans (16.8 years), with Hispanic-Americans (16.0 years) between these two groups. No gender differences were found for age of initiation for any ethnic group. Early age of initiation in Euro-Americans was associated with greater dependence on tobacco, reduced motivation to quit, less likelihood of quitting in the next 12 months, and a number of other health risk factors including lower self-reported physical activity, greater intake of high-fat foods, more favorable attitudes toward illegal drugs, increased likelihood of binge drinking, and less reported use of seat belts. Relationships between early age of initiation and other unhealthy behaviors were less consistent for African-Americans and for neither African-Americans nor Hispanics did age of initiation predict smoking status at 1-year follow-up.
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PURPOSE: To describe information needs of elderly postsurgical cancer patients. Few reports have described learning needs of postsurgical cancer patients during the initial weeks after hospitalization. Responding to information needs during the transition to home is important for helping patients and families to appropriately manage illness. DESIGN: Descriptive, using records kept for patients assigned to the experimental group in a larger study completed in 1996. The sample was 148 American patients surgically treated for a new diagnosis of prostate, breast, gastrointestinal, lung, or head and neck cancer. Information needs were identified from topics addressed by advanced practice nurses during 4-week episodes of home care. METHODS: Content analysis of 3,280 statements of teaching interventions. FINDINGS: Teaching themes were instructing on postoperative self-care, advising on symptom management, clarifying the illness experience, discussing psychological responses, and preparing patients and families to coordinate follow-up care. Topics included describing the expected course of illness, informing about community resources, identifying events that require physician notification, and advising on pain management. Topic emphasis varied by site of cancer. CONCLUSIONS: Information needs of elderly postsurgical cancer patients during transition from hospital to home are extensive. Teaching interventions ranged from giving concrete instructions about care of a surgical wound to interpreting complex information about options for cancer treatment. Elderly postsurgical cancer patients need informational support during the transition from hospital to home.
OBJECTIVE: The purpose of this study was to measure the content and comprehensiveness of pregnancy specific smoking cessation strategies within managed care organisations (MCOs) responding affirmatively to the national 1997-98 Addressing Tobacco in Managed Care (ATMC) survey. DESIGN: This cross sectional follow up study consisted of a fax survey sent to medical directors and a 37 question telephone survey of program overseers about the smoking cessation strategy. SUBJECTS: 147 MCOs identifying a pregnancy specific smoking cessation strategy on the 1997-98 ATMC survey served as the initial sample; 88 MCOs of 128 eligible plans completed both components, with a response rate of 69%. RESULTS: Pregnancy specific smoking cessation strategies varied. 40% of respondents used the Agency for Health Care Policy and Research guidelines for clinical smoking cessation to design their strategy. Strategies included self help materials, quit classes, telephone support and brief counselling by providers, linkages to quality improvement efforts, and use of patient databases for outreach. Only 42% offered a postpartum relapse prevention element. Lack of patient interest, competing clinic priorities, and the lack of a smoker identification system were the most problematic barriers to implementing strategies, common to at least a quarter of respondents. A majority ranked best practice manuals and web site linkages as the most useful form of technical assistance, followed by peer-to-peer counselling, regional workshops, newsletters, on-site assistance, and national conferences. CONCLUSIONS: The survey provides the first profile of prenatal tobacco treatment strategies in managed care. While design limitations prevent generalisation of these results to all MCOs, such information can help guide technical assistance to plans interested in reducing smoking among pregnant women.
BACKGROUND: Early age of initiation is a significant risk factor for long-term dependent smoking and may also relate to other unhealthy behaviors and increased likelihood of illness, independent of duration of smoking. METHODS: The current study assessed age of initiation in relation to cigarette dependence, interest in quitting, social environment pertaining to smoking, behavioral risk factors, and current health problems. Subjects were 2120 current daily smokers in 24 worksites in the Minneapolis/St. Paul, Minnesota, metropolitan area. RESULTS: Findings were surprisingly consistent with early age of initiation predicting more dependent smoking, less interest and confidence in ability to quit, poorer diet, less use of seat belts, more illness and hospitalization, and greater likelihood of smoking among partner/spouse, friends, and co-workers. CONCLUSIONS: The overall strength of the findings was unexpected. Early initiation of regular smoking predicted a significant constellation of risk factors throughout adulthood. Interventions that significantly delay smoking onset, even in the absence of permanent prevention, could have important public health implications.
Neoplastic involvement of the pericardium resulting in an effusion and subsequent tamponade is an emergency requiring prompt decompression, generally safely accomplished by subxiphoid pericardiectomy. However, the current case report describes a patient with florid pericardial tamponade who underwent surgical decompression with transient hemodynamic improvement, who then rapidly developed progressive, heart failure and death. This paradoxical response to pericardial decompression, similar to that seen occasionally with pericardiectomy in constrictive pericarditis, may be more frequent than currently appreciated. Its cause may relate to the sudden removal of the chronic external ventricular support from the effusion resulting in ventricular dilatation and failure.
Opportunistic infections that arise in the immunocompromised host are a major cause of morbidity and mortality. Although bacterial infections are more frequent, invasive fungal infections occur commonly and carry higher risks in these immunocompromised patients. Newer antifungal agents, along with an occasional pulmonary resection, have improved the treatment options and the survival from invasive fungal infections in immunocompromised patients.