Longitudinal current losses in rf linear accelerators.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Brown.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This paper describes a study which aimed to explore the present and ideal role of the nurse teacher in the clinical area from the perspective of: nurse teachers; ward sisters/charge nurses; staff nurses and students nurses undertaking the 'traditional' and Project 2000 programmes of training. The study adopted a qualitative design. Findings from this study demonstrate that the clinical role of the nurse teacher lacks clarity, however, clear criteria emerged as to how trained nurses and student nurses perceived the ideal role. Nurse teachers' role in assuring the quality of the clinical learning environment emerged as a major area of criticism. It was suggested that, if nurse teachers adopted a clinical role that was primarily concerned with supporting clinically based nurses in their teaching role, this served to assure the quality of students' clinical learning experience. In conclusion, it is suggested that for nurse teachers to meet the needs of trained nurses and student nurses in the clinical area, the role must be diverse and flexible. Attempts to prescribe a unimodel approach to deliver the service should be avoided. Rather, the role must be negotiated between teachers, clinical nurses and students, and constructed in a way that best meets the needs of all parties concerned.
Explore the source record for details and available documents.
A major aspect of a clinical trial is the ability to successfully recruit patients. There is a paucity of information concerning the nuances of recruiting study patients, especially those from minority communities. As minorities generally have been underrepresented in the health-care system, they may be less likely to participate in clinical trials or other studies. Thus, a strategy is needed to overcome this potential shortfall. One of our solutions has been the development of a community network to help disseminate information about our program. We believe that a key aspect has been the involvement of community members during pre-trial planning, community awareness programs, and our Community Advisory Panel. We also believe that it may be a major error to bring a health-care initiative unannounced into a targeted community without extensive pre-program planning in cooperation with that community. As our community awareness scheme suggests (Figure), there are many possible avenues to heighten awareness about a health-care program. While the church remains an important institution for religious and cultural activities in the African-American community, we have found that the news, television, and radio media also can be a powerful source for spreading awareness. Thus, we recommend creating awareness about an initiative through a "grassroots" approach of church and community organizations, along with a global approach through news, television, and radio media. As part of the awareness promotion campaign, it must be emphasized that the study is safe and provides benefits to enrollees. The success of health programs is largely dependent on community acceptance, which must be established in the pre-program planning stages of the initiative. This concept of obtaining community approval and acceptance prior to program initiation is not a new one, nor does it exclusively apply to the African-American community. Community leaders and members need to have a vested interest in such a program and a sense of empowerment. Through this type of communication, patient enrollment and community satisfaction can be substantial. Such success can serve as a springboard for other targeted health-care studies or programs in high-risk communities.
Short-term outcome in very low birthweight babies has never been closely examined in Papua New Guinea. A cohort of neonates born over a year at Port Moresby General Hospital was followed from birth to death or discharge. Intrauterine growth retardation was an important contributor to low birthweight. Simple, inexpensive care resulted in respectable survival figures. Improving antenatal surveillance will have much more impact in reducing mortality in this group in the future than trying to emulate sophisticated and costly western neonatal care.
The clinical experience of human immunodeficiency virus (HIV) + patients treated with oral atovaquone for acute Pneumocytstis carinii pneumonia (PCP) under a Treatment Investigational New Drug (IND) protocol (mild or moderate PCP) and an Open-Label Study protocol (severe PCP) was evaluated. A total of 940 patients intolerant of or unresponsive to trimethoprimsulfamethoxazole were enrolled from private practices, clinics, and institutional HIV treatment centers in the United States. Demographics data and the history and severity of PCP were collected at enrollment. The number of therapy days, adverse experiences, clinical response to therapy, and mortality were collected at day 21. Reporting of serious, unexpected adverse experiences attributable to therapy was required. Of the 760 (96%) patients with mild to moderate disease for whom follow-up observation was complete, 591 (78%) responded clinically to treatment, 177 patients (23%) discontinued treatment prematurely, and 50 patients (7%) died. Of the 140 patients (95%) with severe PCP with follow-up data, 79 (56%) responded to treatment, 45 (32%) discontinued treatment early, and 53 patients (38%) died. Adverse events that resulted in temporary or permanent discontinuation of therapy included diarrhea, vomiting, elevated liver enzyme levels, nausea, and fever. No serious unexpected adverse events attributable to the drug were reported. The treatment IND mechanism enabled a large number of patients with acute PCP to be treated with this experimental therapy while the drug was under regulatory view.
p13suc1 binds to p34cdc2 kinase and is essential for cell cycle progression in eukaryotic cells. The crystal structure of S.pombe p13suc1 has been solved to 2.7 A resolution using data collected at the ESRF source, Grenoble, from both native crystals and crystals of a seleno-methionine derivative. The starting point for structure solution was the determination of the six selenium sites by direct methods. The structure is dominated by a four-stranded beta-sheet, with four further alpha-helical regions. p13suc1 crystallizes as a dimer in the asymmetric unit stabilized by the binding of two zinc ions. A third zinc site stabilizes the higher-order crystal packing. The sites are consistent with a requirement for zinc during crystal growth. A likely site for p13suc1-protein interaction is immediately evident on one face of the p13suc1 surface. This region comprises a group of conserved, exposed aromatic and hydrophobic residues below a flexible negatively charged loop. A conserved positively charged area would also present a notable surface feature in the monomer, but is buried at the dimer interface. p13suc1 is larger than its recently solved human homologue p9CKS2, with the extra polypeptide forming a helical N-terminal extension and a surface loop between alpha-helices 3 and 4. Notably, p13suc1 does not show the unusual beta-strand exchange that creates an intimate p9CKS2 dimer. p13suc1 cannot oligomerize to form a stable hexamer as has been proposed for p9CKS2.
Explore the source record for details and available documents.
OBJECTIVE: To report a case of a newborn female infant noted to have features of the megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) with the additional features of hydrometrocolpos and segmental colonic dilatation and review the literature. METHODOLOGY: The details of the case were collated and compared with the previous published experience with this condition. RESULTS: Thus far there have been 58 previous cases of MMIHS described, only four of which have had colonic dilatation. A number of concurrent anomalies have been described, but not the hydrometrocolpos or dysmorphic features seen in this patient. CONCLUSION: This case appears to be MMIHS with additional features not previously recorded.
To better understand risk factors for Alzheimer's disease and vascular dementia, demographic, medical, and other epidemiological factors were compared for 83 African-American women with Alzheimer's disease and 46 with vascular dementia. Overall, the risk-factor profiles for Alzheimer's disease and vascular dementia were similar to those in other studies. However, Alzheimer's patients had a high frequency of hypertension and a relatively high frequency of diabetes mellitus. The presence of such risk factors raises the possibility that there is a vascular component to the dementia in these African-American women with Alzheimer's disease. Neuropathological studies are needed to help answer this question.
The demographic and clinical features of severe malaria in children on the south coast of Papua New Guinea have never been clearly documented. This prospective study sought to define the associations between ethnic origin, domain, age, nutritional status and severe malaria in this group and to assess significant clinical features, evaluate the use of a coma score as a prognostic indicator in cerebral malaria and to determine the ultimate outcome. Twenty patients with severe malaria (17 cerebral malaria and 3 severe anaemia) were studied. Their mean age of 4.96 years was significantly greater than that of matched controls with uncomplicated. Plasmodium falciparum infection with mean age 3.79 years (0.02 < p < 0.05). Nutritional status was not a significant independent risk factor when controlled against inpatients with other diagnoses. Low coma scores (Adelaide scale 4/14 or less) sensitively predicted the risk of dying vs survival. The mortality of 18% was comparable with other series. Current standard treatment with quinine and Fansidar was effective and no early recrudescence was encountered in the survivors. The degree of intermarriage and migration between regions precluded firm conclusions from being drawn as to the relevance of ethnic and geographical factors in the epidemiology of severe malaria in this region.
PURPOSE: These studies were designed to develop an orthotopic model for human bladder cancer and to isolate variant metastatic cell lines. MATERIALS AND METHODS: The human bladder cancer cell line 253J was implanted into the muscular wall of the bladder of athymic nude mice. By in vivo recycling, we selected for 2 variant cell lines: 253J B-V, a bladder line isolated after 5 serial passages in the bladder, and 253J lung-IV, established from a lung tumor nodule that was recycled through the bladder. RESULTS: These 2 cell lines showed enhanced tumorigenicity, as measured by a decreased latent period, and rapid growth as compared with the parental cell line. Moreover, orthotopic implantation of these cell lines resulted in metastasis to the lungs. These in vivo-selected, metastatic cell lines exhibited unique karyotypic alterations, increased anchorage-independent growth, overexpression of basic fibroblast growth factor, altered expression of adhesion molecules and the ability to migrate through Matrigel. CONCLUSIONS: This reproducible model of human bladder cancer offers the opportunity to study cellular properties associated with tumor progression and metastasis and is suitable for the evaluation of new therapeutic strategies for invasive bladder cancer.
Explore the source record for details and available documents.
Analyses were done on a human type-IV cyclic AMP (cAMP) phosphodiesterase (hPDE-IVA-h6.1) expressed in an engineered strain of Saccharomyces cerevisiae. This strain (YMS6) expressed soluble PDE activity, together with an insoluble activity which was not released by re-homogenization, treatment with high-ionic-strength solutions or with the detergent Triton X-100. Pellet and soluble PDE activities were typical of type-IV PDE. They were cAMP-specific, insensitive to the addition of either cGMP (1 microM) or Ca2+/calmodulin, and inhibited by rolipram. Thermostability studies showed both activities to decay as single exponentials, indicating the presence of homogeneous PDE protein species in each fraction. Pellet PDE activity was more thermostable than the soluble enzyme. Mg2+ and Mn2+ dose-dependently increased PDE activity and reversed the inactivating effect of EDTA.h6.1 was engineered to express a C-terminal five-histidine motif (h6.1his5). This allowed purification of the PDE to apparent homogeneity in a simple two-step process involving a rolipram affinity column and a Ni2(+)-chelate column. A single monomeric protein of subunit molecular mass approximately 73 kDa and native molecular mass approximately 74 kDa resulted after a approximately 53000-fold purification. This exhibited a Km for cAMP of 8 microM, a true Vmax. of 0.8 mumol of cAMP hydrolysed/min per mg of PDE protein, a kcat. of 3702 s-1, and a value of the specificity constant kcat/Km of 4.6 x 10(8) M-1.s-1, the last implying a diffusion controlled reaction. Rolipram (Ki 0.4 soluble; 0.7 microM pellet) and 3-isobutyl-1-methylxanthine (Ki 15 soluble; 19 microM pellet) served as simple competitive inhibitors for both soluble and pellet forms of h6.1, respectively.
It has recently been established that rat heart mitochondria contain two isoforms of carnitine palmitoyltransferase I (CPT I), the minor 88-kDa variant being identical to liver CPT I (L-CPT I) and the dominant 82-kDa form resembling the skeletal muscle enzyme (M-CPT I) (Weis, B. C., Esser, V., Foster, D. W., and McGarry, J. D. (1994) J. Biol. Chem. 269, 18712-18715). To quantify the functional contribution of L-CPT I to overall CPT I activity in heart mitochondria a selective inhibitor of the former was needed. The dinitrophenol analog of 2[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylic acid (etomoxir) (DNP-Et) was found to have this property. When liver and skeletal muscle mitochondria were exposed to DNP-Et in the presence of ATP and CoASH, the DNP-Et-CoA formed completely inhibited liver CPT I while leaving the muscle enzyme unaffected. Similar treatment of heart mitochondria blocked only the L-CPT I component. This had the effect of shifting the apparent Km for carnitine from approximately 200 to approximately 500 microM and the I50 value for malonyl-CoA (the concentration needed to suppress enzyme activity by 50%) from approximately 0.18 to approximately 0.06 microM, i.e. the heart system now behaved exactly the same as that from skeletal muscle. Taking the Km for carnitine of L-CPT I and M-CPT I to be 30 and 500 microM, respectively, it could be calculated that the former contributes approximately 2% to the total CPT I in heart. When the 82-kDa CPT I isoforms of heart and skeletal muscle were labeled with [3H]etomoxir and then exposed to trypsin, the fragmentation patterns obtained were identical and quite distinct from that given by CPT I from liver. We conclude that (i) DNP-Et, unlike other agents of the oxirane carboxylic acid class, has remarkable inhibitory selectivity for L-CPT I over M-CPT I; (ii) the previously puzzling observation that rat heart CPT I displays kinetic characteristics intermediate between those of the enzymes from liver and skeletal muscle is entirely accounted for by the low level expression of L-CPT I in the cardiac myocyte; and (iii) the dominant 82-kDa CPT I isoform in heart is identical to the muscle enzyme. The data reaffirm that, in contrast to CPT II, CPT I exists in at least two isoforms and that both are present in rat heart.
Explore the source record for details and available documents.
Even though hypoxia is a major risk factor for death in children with acute respiratory infection in developing countries, oxygen is not part of first line treatment. Because oxygen is not readily available in developing countries it tends to be given to the most seriously ill children, whose outcome is poor. Oxygen might be useful if given earlier in the course of the disease. Clinical signs are not clear cut, however, though the presence of cyanosis and grunting together with a raised respiratory rate can significantly increase the detection of hypoxaemia. A simple oximeter would make detection easier, and oxygen concentrators are more cost effective than bottled oxygen. Ideally oxygen should be given to children in the early stages of clinical pneumonia to prevent deterioration.