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M Ainsworth

Publications and source records attributed to M Ainsworth.

At least 19 recordsLinked to original sources
PubMed2001

Private investment in AIDS vaccine development: obstacles and solutions.

The development of vaccines for the prevention of AIDS, malaria, tuberculosis, and other diseases requires both public and private investment. Private investment, however, has been far lower than might have been hoped, given the massive human toll of these diseases, particularly in the poorest countries. With a view to understanding this situation and exploring potential solutions, the World Bank AIDS Vaccine Task Force commissioned a study on the perspectives of the biotechnology, vaccine, and pharmaceutical industries regarding investment in research and development work on an AIDS vaccine. It was found that different obstacles to the development of an AIDS vaccine arose during the product development cycle. During the earlier phases, before obtaining proof of product, the principal barriers were scientific. The lack of consensus on which approach was likely to be effective increased uncertainty and the risks associated with investing in expensive clinical trials. The later phases, which involved adapting, testing, and scaling up production for different populations, were most influenced by market considerations. In order to raise the levels of private research and development in an AIDS vaccine there will probably have to be a combination of push strategies, which reduce the cost and scientific risk of investment, and pull strategies, which guarantee a market.

AIDS Vaccines↗
PubMed2001

Setting performance standards for medical practice: a theoretical framework.

BACKGROUND: The assessment of performance in the real world of medical practice is now widely accepted as the goal of assessment at the postgraduate level. This is largely a validity issue, as it is recognised that tests of knowledge and in clinical simulations cannot on their own really measure how medical practitioners function in the broader health care system. However, the development of standards for performance-based assessment is not as well understood as in competency assessment, where simulations can more readily reflect narrower issues of knowledge and skills. This paper proposes a theoretical framework for the development of standards that reflect the more complex world in which experienced medical practitioners work. METHODS: The paper reflects the combined experiences of a group of education researchers and the results of literature searches that included identifying current health system data sources that might contribute information to the measurement of standards. CONCLUSION: Standards that reflect the complexity of medical practice may best be developed through an "expert systems" analysis of clinical conditions for which desired health care outcomes reflect the contribution of several health professionals within a complex, three-dimensional, contextual model. Examples of the model are provided, but further work is needed to test validity and measurability.

Clinical Competence↗
PubMed2000

Breaking the silence: setting realistic priorities for AIDS control in less-developed countries.

The AIDS pandemic is a human tragedy that is threatening development in the poorest countries. There is no cure or vaccine, but the tools to control the epidemic already exist. Nevertheless, there are few examples of national AIDS control programmes that have had an impact on the epidemic. We (an economist and a planner) attribute this to the reluctance of governments to confront AIDS and a failure to prioritise activities in the face of severe financial and administrative constraints. When implementation capacity is weak, expanding the number of activities may not improve programme effectiveness. Rather, by implementing a smaller, core set of the most cost-effective activities on a national scale, policymakers could have a huge effect on the overall epidemic in a sustained way and provide a foundation for expansion. We propose three core priorities for AIDS control in poor countries for prevention, treatment, and mitigation of the impact.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Ligation of ICAM-1 on endothelial cells leads to expression of VCAM-1 via a nuclear factor-kappaB-independent mechanism.

ICAM-1 is an Ig-like cell adhesion molecule expressed by several cell types, including the endothelium. Cross-linking of ICAM-1 on the surface of different cell types has previously been shown to cause an increase in cellular activation within the cytoplasm. In this study, we have compared signaling events following ligation of ICAM-1 by cross-linking with mAbs with events after activation of HUVEC by TNF. ICAM-1 cross-linking caused activation of Erk-1 and the AP-1 transcription factor complex, without any increase in NF-kappaB activity, in contrast to TNF stimulation. Transcription of VCAM-1 mRNA was observed by reverse-transcriptase PCR after ICAM-1 cross-linking, with no associated transcription of E-selectin. This was reflected by the presence of VCAM-1 protein after immunoprecipitation, without E-selectin expression, in ICAM-1 cross-linked cells. In contrast, mRNA and protein for both VCAM-1 and E-selectin were observed in TNF-treated HUVEC, as expected. Addition of the MEK (MAP/Erk kinase) inhibitor PD98059 reduced expression of VCAM-1 after ICAM-1 cross-linking, suggesting that the Erk pathway is involved in ICAM-1-mediated VCAM-1 expression. In conclusion, ICAM-1-induced expression of VCAM-1 represents a pathway for adhesion molecule up-regulation that is distinct from the TNF-induced pathway. It may be similar to the IL-4 pathway or it may represent a novel pathway.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Rectal dialysate and fecal concentrations of neutrophil gelatinase-associated lipocalin, interleukin-8, and tumor necrosis factor-alpha in ulcerative colitis.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is a newly described neutrophil lipocalin that may bind the proinflammatory bacterial tripeptide N-formylmethionyl-leucyl-phenylalanine. In situ hybridization and immunohistochemical studies have shown a strong NGAL expression in colonocytes and neutrophils in ulcerative colitis (UC). Because NGAL is highly protease resistant, it should be ideal for in vivo fecal and dialysate studies. Our aim was to investigate the potential of NGAL as a disease activity marker in UC and to compare it with IL-8 and TNF-alpha. METHODS: Twenty-three patients with UC, 14 with Crohn's disease (CD), 19 patients with acute infectious enterocolitis, and 20 healthy controls were included. The disease activity of UC and CD was scored semiquantitatively. Concentrations of NGAL, IL-8, and TNF-alpha were determined in rectal dialysis fluid, feces, and serum using sandwich enzyme-linked immunosorbent assays. The total protein concentration in feces and dialysate fluid was measured, and the amount of markers was expressed as ng/mg protein. RESULTS: In healthy controls and non-IBD (irritable bowel disease) colitis, the median values for NGAL in feces were 183 ng/mg protein and 546 ng/mg protein (p < 0.01), respectively. When separating UC into clinical activity groups (remission, mild/moderate, and severe disease activity) the corresponding values of NGAL were 442 ng/mg (p > 0.05), 605 ng/mg (p < 0.02), and 3646 ng/mg (p < 0.001, compared with controls), respectively, and in quiescent colonic CD 368 ng/mg (p > 0.05) and in active stages 751 ng/mg (p < 0.01). NGAL levels in dialysis fluid listed in the same order were: 11 ng/mg for controls, 71 ng/mg (p > 0.05) for non-IBD colitis, 100 ng/mg (p < 0.02), 179 ng/mg (p < 0.01), and 2053 ng/mg (p < 0.001) for UC, and 14 ng/mg (p > 0.05) and 121 ng/mg (p < 0.02) for CD, respectively. Serum NGAL concentrations did not differ between UC and CD in quiescent versus active stages. A significant increase of NGAL in both feces and dialysate with increasing disease activity of UC was found (p = 0.02 and p = 0.003, respectively). CONCLUSIONS: The NGAL content in rectal dialysate and particularly in feces seems to be a reliable marker for severe disease activity in UC, whereas serum NGAL concentrations do not reflect disease activity.

Acute-Phase Proteins↗
PubMed1996

Economic aspects of child fostering in Cote d'Ivoire.

"This paper examines the economic determinants of child fostering decisions in Cote d'Ivoire [Ivory Coast], where in 1985 one-fifth of non-orphaned children age 7-14 were living away from both natural parents. The economic determinants of both sending and receiving decisions are examined separately and evaluated with respect to their support for child labor and human capital explanations. The determinants for both sides of the fostering market are then estimated simultaneously, using a model of friction developed by Rosett (1959), so that the symmetry of fostering determinants can be formally tested."

Adolescent↗
PubMed1994

Internal medicine preceptorships: three successful programs.

Undergraduate medical education is evolving to include community physicians in the training of students in the outpatient setting. The task of designing and implementing such preceptorships can be hindered by financial, institutional, and logistic factors. Nonetheless, several institutions have successfully begun such preceptorships, even in the absence of major federal or philanthropic funding. In this article, three institutions offer suggestions for overcoming the factors hindering the development of a successful preceptorship.

Education, Medical, Undergraduate↗
PubMed1989

Intestinal permeability of 51Cr-labelled ethylenediaminetetraacetic acid in patients with Crohn's disease and their healthy relatives.

An increased intestinal permeability has been proposed as an aetiologic factor in Crohn's disease. The 24-h urinary excretion of 100 muCi 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) was used to test the permeability in 15 patients with Crohn's disease and in 20 healthy first-degree relatives, who are known to have a genetic predisposition to inflammatory bowel disease. Twenty-eight healthy persons not related to patients with inflammatory bowel disease served as control material. The 51Cr-EDTA excretion of the relatives (range, 0.98%-3.87%; median, 1.935%) was not significantly higher than that of the controls (range, 1.17%-3.26%; median, 1.950%), whereas patients with Crohn's disease had a significantly higher excretion (range, 1.64%-8.86%; median, 2.940%) than both the relatives and the controls. Among patients the increased excretion was found only if the small intestine was involved. We conclude that 1) as a group, patients with Crohn's disease in the small intestine have an increased intestinal permeability, in contrast to their healthy relatives, who have a normal permeability; 2) a considerable overlap of the results of the 51Cr-EDTA test was found between the groups studied, and the test is not suitable for evaluating individual patients; 3) our results do not support the hypothesis of an increase in intestinal permeability as an aetiologic factor in Crohn's disease.

Adolescent↗
PubMed1989

Effects of oleic acid and oleyl alcohol on cholecystokinin and secretin in plasma and pancreatobiliary secretion.

To evaluate the importance of the terminal carboxy group of the oleic acid molecule in the release of secretin and cholecystokinin (CCK) to plasma, six normal persons were stimulated twice with duodenal perfusates containing either 20 mM oleic acid or 20 mM oleyl alcohol. Oleic acid increased the pancreatic secretion of bicarbonate and amylase and the concentrations of secretin and CCK in plasma and provoked gallbladder emptying. Oleyl alcohol only increased the amylase output slightly, but significantly. It is concluded that the carboxy group of the fat molecule has an important role in triggering the release of secretin and CCK to plasma.

Adult↗
PubMed1988

Effect of intravenous immunoglobulin on a spontaneous inhibitor to factor VIII.

A 71-year-old woman with a spontaneous anti-factor VIII inhibitor fractured her right wrist and 2 months later her left femur. She received treatment with porcine factor VIII for the first fracture and developed a secondary anti-porcine antibody response (from 10 to 200 Bethesda units). Following the second fracture she received intravenous immunoglobulin (i.v. IgG) (0.4 g/kg day for 5 days) in an attempt to reduce antibody activity. Despite further treatment with porcine factor VIII, the antibody level declined instead of rising as expected and the anti-human antibody activity also declined. We were not able to demonstrate neutralizing activity to her antibody but did demonstrate a reduced helper: suppressor ratio and reduced B-cell numbers and function after treatment with i.v. IgG. These changes were transient and as B-cell function improved over the following 4 months, her anti-human activity returned toward its previous level. Anti-porcine activity remained at its previous low level. We speculate that one of the mechanisms of action of i.v. IgG may be a direct cellular effect influencing both T-suppressor and B-lymphocyte function.

Aged↗
PubMed1987

A direct effect of glucocorticoid hormones on the ability of human and murine macrophages to control the growth of M. tuberculosis.

Recombinant murine Gamma interferon (rIFN-gamma) causes powerful inhibition of M. tuberculosis by murine peritoneal macrophages. This inhibition is totally abrogated by glucocorticosteroid hormones. In contrast, glucocorticoids do not oppose the weak inhibition of M. tuberculosis by human macrophages which can be induced with human rIFN-gamma, nor do they reduce the effect in this system of 1,25-(OH)2 vitamin D3. However, glucocorticoid hormones do decrease the baseline inhibition of M. tuberculosis exerted by monocytes from some normal human donors without any preincubation in an activating stimulus. Thus there is a steroid-sensitive anti-mycobacterial mechanism in human macrophages, but IFN-gamma is not the lymphokine which induces it. We suggest that this mechanism may be important for protection and steroid-induced reactivation, and deserves further study. On the other hand, the IFN-gamma and vitamin D3 pathway may be more relevant to immunopathology.

Animals↗
PubMed1986

Heat-treated NHS factor VIII concentrate in the United Kingdom--a preliminary study.

Three patients who have been given intermediate purity NHS heat-treated factor VIII concentrate have been followed prospectively for 7-10 months. None had previously received more than six donor units of blood products containing factor VIII. There were no clinical side effects from concentrate administration, haemostasis was satisfactory and no patient developed clinical or laboratory evidence of hepatitis or HTLV III/LAV infection. Heat treatment resulted in the loss of slightly more than 20% of factor VIII activity but in vivo recovery of factor VIII and half disappearance times were within the expected range.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Activation of macrophages to inhibit proliferation of Mycobacterium tuberculosis: comparison of the effects of recombinant gamma-interferon on human monocytes and murine peritoneal macrophages.

When cultured in 20% heat-inactivated human serum, human monocytes from seven donors were not on average significantly different from non-activated murine peritoneal cells (cultured simultaneously and in an identical manner) in their ability to inhibit BCG and, when calculated relative to growth of bacilli in the same medium without macrophages, to enhance the growth of Mycobacterium tuberculosis. Recombinant gamma-interferon caused marked inhibition of virulent M. tuberculosis by murine (BALB/c) peritoneal macrophages. This effect was seen, whether the cells were cultured in 10% fetal calf serum or in 20% heat-inactivated normal human serum, with or without the addition of iron supplements. However, unlike murine cells, the addition of crude lymphokine or recombinant gamma-interferon to human monocytes caused only weak inhibition of M. tuberculosis, and in some instances, gamma-interferon caused enhancement of growth of the bacilli. Monocytes were only slightly more effective if precultured for 4-8 days before the addition of the activating stimulus. This relative failure to develop anti-mycobacterial mechanisms occurred in spite of the activation of the cells as shown by a massive increase in reduction of nitro-blue tetrazolium inducible by phorbol myristate acetate.

Animals↗