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PubMed1989

The role of arterial wall injury in atherogenesis and arterial thrombogenesis.

Accumulating mainly experimental evidence from research of the last 3 decades shows that many types of arterial wall injury can accelerate and intensify the development of atherosclerosis in arteries exposed to chronic hyperlipemia by increasing the permeability of their endothelium for plasma lipoproteins, proteins and several types of smooth muscle mitogens (including soluble platelet-derived growth factor). Of the numerous artery-injuring agents studied experimentally today only those that can be proven to operate in humans at concentrations and durations of action that injure animal arteries can be accepted as capable of playing a role in human atherogenesis. Seven such groups of agents can be recognized at present: blood turbulence, hypertension, certain viruses, metabolic disturbances (including hyperlipemia), certain immune insults, exogenous chemicals, and obstruction of adventitial lymphatics. Most of the above agents cause various degenerative changes in individual endothelial cells or open interendothelial junctions, and they seem to promote the penetration of plasma macromolecules into the wall in 3 different ways: directly through the altered endothelial cytoplasm, through opened interendothelial junctions or through transport in the cytoplasm of immigrating monocytes. None of the commonly occurring injury agents produce complete endothelial denudation of wide areas of the arterial cylinders. New findings from the transmission electron microscopic study of step-serial sections of human arteries obtained under conditions minimizing artificial endothelial loss indicate that endothelial denudation accompanied by platelet adherence and aggregation does not occur over early myoproliferative lesions but occasionally develops over small areas of advanced plaques with mostly necrotic or damaged caps and is, therefore, not an initiating event but a late complication of atherosclerosis. Light microscopic serial section studies of human thrombosed vessels in several centers reveal that thrombogenesis in most human atherosclerotic arteries is initiated by a severe structural injury of the cap of advanced plaques that leads to a microscopic break of the plaque surface through which some blood can enter the plaque interior before it is sealed by a thrombus.

Arteries↗

PubMed1997

Aminoguanidine and the prevention of leukocyte dysfunction in diabetes mellitus: a direct vital microscopic study.

1. Defective leukocyte-endothelial interactions are observed in experimental diabetes mellitus. The present study investigated the effect of aminoguanidine, an inhibitor of advanced glycation end products formation, on leukocyte-endothelial interactions in alloxan-induced diabetic rats. 2. In rats anaesthetized with sodium pentobarbitone, the internal spermatic fascia was exteriorized and the microcirculation was observed by a closed-circuit TV coupled to a microscope. The number of leukocytes rolling along the venular endothelium and sticking to the vascular wall was determined after topical application of zymosan-activated plasma (1 mg ml(-1)), as well as the number of adherent and migrated cells after an irritative stimulus (carrageenan 100 microg). 3. The diabetic state decreased the number of rolling, sticking and migrated leukocytes. Pretreatment of diabetic animals with aminoguanidine (250 mg kg(-1) day(-1), for 18 days) normalized these values. To be effective, aminoguanidine had to be administered chronically, starting treatment before induction of the diabetic state. 4. The preventive effect was unrelated to the number of circulating leukocytes, or to the hyperglycaemia or to the hyperosmolality secondary to hyperglycaemia. 5. A non-dialyzed (>12,000-Mr) material in plasma from diabetic, but not normal animals, decreased the number of rolling, sticking and migrated leukocytes in recipient rats. This effect was completely abolished by chronic treatment of diabetic plasma donors with aminoguanidine. 6. The results suggest that a protein modified by glycosylation (>12 kDa) is associated with leukocyte dysfunction in diabetes mellitus and that the ability of aminoguanidine to prevent such dysfunction is related to an inhibitory effect on advanced glycation end products formation.

Alloxan↗

PubMed1998

Dynabeads plus 3 M Petrifilm HEC versus Vitek Immunodiagnostic Assay System for detection of E. coli O157 in minced meat.

The potentially low infective dose of Escherichia coli O157 makes it necessary to be able to detect low numbers in food, and the lack of sensitivity of direct plating has led to the development of various enrichment and detection methods. Until now, the most selective procedure for detection of E. coli O157 isolates was the immunomagnetic separation (IMS) method. The number of sorbitol non-fermenting micro-organisms other than E. coli O157 that adhere non-specifically to the magnetic beads hampers the application of IMS. The use of IMS in conjunction with 3 M Petrifilm-HEC yielded EHEC O157 in 21 of 165 samples of minced meat (12.7%). Without advance application of IMS, Petrifilm plates often yield confluent growth and colonies too numerous to count. The Vitek Immunodiagnostic Assay System (VIDAS-ECO) showed good sensitivity when testing artificially contaminated beef samples, but only four of 21 naturally contaminated samples were recognized. The addition of 3 M Petrifilm to IMS resulted in less growth of contaminants and eliminated much of the need to test presumed colonies for confirmation. The combination of IMS and 3 M Petrifilm-HEC is a fast and efficient screening procedure for E. coli O157 in minced meat.

Animals↗

PubMed2004

Essential benefits of nucleoside analogue regimens in failing therapy.

Since the introduction of highly active antiretroviral therapy, nucleoside and more recently nucleotide reverse transcriptase inhibitors (NRTIs) have provided a highly effective backbone to antiretroviral regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Nonetheless, treatment failure can result from poor adherence, unfavourable pharmacokinetics, advanced disease or infection with a drug-resistant virus. Recent data have also indicated a high risk of virological failure with triple NRTI regimens, reflecting overall lower potency compared to combinations of NRTIs with either NNRTIs or PIs. Resistance mutations emerging upon failure can cause extensive cross-resistance among available NRTIs, and potentially affect susceptibility to newly developed antiretroviral drugs. However, despite the emergence of resistance, NRTIs can retain significant antiviral activity in treatment-experienced patients. This may reflect residual direct viral load suppression, as well as indirect effects related to impaired viral fitness of NRTI-resistant mutants and antagonist interactions between resistance mutations.

Antiretroviral Therapy, Highly Active↗

PubMed2026

Critical insights on the application of the theory of planned behaviour to food handlers' food safety practices.

Foodborne diseases remain a significant public health concern, often linked to unsafe food-handling practices. The Theory of Planned Behaviour (TPB) is widely used to predict and explain food safety behaviours, yet its application in this field has not been systematically and in-depth evaluated. This review evaluated how the TPB has been applied to study food handlers' behaviour, focusing on methodological approaches, use of the TACT (Target, Action, Context, and Time) framework, validity, elicitation studies, and reliability. Seventeen studies were included following a systematic search of four databases (Scopus, Web of Science, Wiley Online Library, and Taylor & Francis Online). Data were extracted on behaviour definition, aim of study, main findings, use of indirect and direct TPB measures, use of elicitation studies, internal consistency, content validation, analytical methods used, and any extensions to the original TPB framework. Key elements related to adherence to core TPB principles and measurement practices were extracted using a Checklist. Most studies used direct measures of TPB constructs, and only a few reported procedures for content validation. Considerable variability was found in the reporting of key measurement and psychometric practices. Five studies fully applied the TACT framework, while nine incorporated additional factors such as knowledge and moral norms. Elicitation studies were conducted in five cases where indirect measures were employed. Analytical approaches were mainly based on multiple linear regression, with limited use of more advanced techniques such as structural equation modeling. Twelve studies reported internal consistency results. Overall, the review highlights opportunities to strengthen methodological practices in future TPB research on food safety. Greater attention to conducting and reporting content validation, full application of the TACT framework, reporting of internal consistency, and consistent inclusion of elicitation studies when using indirect measures may enhance transparency, reinforcing the credibility and trustworthiness of research findings. A major methodological limitation of this review was that screening and data extraction were conducted by a single reviewer and no formal quality or risk-of-bias assessment of the included studies was performed. Despite these limitations, the findings provide practical guidance for the development and validation of TPB-based questionnaires and may support more robust food safety research, interventions, and policy initiatives aimed at improving food handlers' practices.

Humans↗

PubMed2001

Public and private providers' quality of care for tuberculosis patients in Kampala, Uganda.

SETTING: The role of the private sector in tuberculosis treatment in developing countries in sub-Saharan Africa is largely unknown. In recent years, many fee-for-service clinics have opened up in Kampala, Uganda. Little is known about the tuberculosis caseload seen in private clinics or the standard of care provided to the patients. OBJECTIVE: To compare the appropriateness of tuberculosis care in private and public clinics, and the extent of the tuberculosis burden handled in the private sector. DESIGN: Cross-sectional survey in private and public clinics treating tuberculosis patients in Kampala, Uganda, during June to August 1999. MEASUREMENTS: Clinics were evaluated for appropriateness of care. This was defined as provision of proper diagnosis (sputum smear microscopy as the primary means of diagnosis), treatment (short-course chemotherapy, with or without directly observed therapy), outcome evaluation (smear microscopy at 6 or 7 months) and case notification in accordance with the Uganda National Tuberculosis and Leprosy Programme. RESULTS: A total of 114 clinics (104 private, 10 public) were surveyed. Forty-one per cent of the private clinics saw three or more new tuberculosis patients each month. None of the public or private clinics met all standards for appropriate tuberculosis care. Only 24% of all clinics adhered to WHO-recommended treatment guidelines. Public clinics, younger practitioners and practitioners with advanced degrees were most likely to provide appropriate care for tuberculosis. CONCLUSION: The private sector cares for many tuberculosis cases in Kampala; however, a new programme that offers continuing medical education is needed to improve tuberculosis care and to increase awareness of national guidelines for tuberculosis care.

Adult↗

PubMed2026

The Lipid Interactome: an interactive and open access platform for exploring cellular lipid-protein interactions.

SUMMARY: Lipid-protein interactions play essential roles in cellular signaling and membrane dynamics, yet their systematic characterization has long been hindered by the inherent biochemical properties of lipids. Recent advances in functionalized lipid probes-equipped with photoactivatable crosslinkers, affinity handles, and photocleavable protecting groups-have enabled proteomics-based identification of lipid interacting proteins with unprecedented specificity and resolution. Despite the growing number of published lipid interactomes, there remains no centralized effort to harmonize, compare, or integrate these datasets. The Lipid Interactome addresses this gap by providing a structured, interactive web portal that adheres to FAIR data principles-ensuring that lipid interactome studies are Findable, Accessible, Interoperable, and Reusable. Through standardized data formatting, interactive visualizations, and direct cross-study comparisons, this resource enables researchers to systematically explore the protein-binding partners of diverse bioactive lipids. By consolidating and curating lipid interactome proteomics data from multiple studies, the Lipid Interactome database serves as a critical tool for deciphering the biological functions of lipids in cellularsystems. AVAILABILITY AND IMPLEMENTATION: This site can be viewed at LipidInteractome.org. All data are available for download. No user information is collected or necessary for data navigation, interaction, or download.

Proteins↗

PubMed2001

beta(2)-Microglobulin modified with advanced glycation end products delays monocyte apoptosis.

BACKGROUND: A local inflammatory reaction to beta(2)-microglobulin (beta(2)m) amyloid deposits by monocytes/macrophages is a characteristic histologic feature of dialysis-related amyloidosis (DRA). Since beta(2)m modified with advanced glycation end products (AGE-beta(2)m) is a major constituent of amyloid in DRA, we tested the hypothesis that AGE-beta(2)m affects apoptosis and phenotype of human monocytes. METHODS: Human peripheral blood monocytes were incubated with or without in vitro-derived AGE-beta(2)m, and their viability, extent of apoptosis, morphology, and function examined over the subsequent four days. RESULTS: AGE-modified but not unmodified beta(2)m significantly delayed spontaneous apoptosis of human peripheral blood monocytes in adherent and nonadherent cultures. The effect of AGE-beta(2)m on monocytes apoptosis was time- and dose-dependent and was attenuated by a blocking antibody directed against the human AGE receptor (RAGE). There was no difference in effect between AGE-beta(2)m and that of AGE-modified human serum albumin. Culture of monocytes with AGE-beta(2)m did not alter membrane expression of Fas or Fas ligand. Monocytes cultured with AGE-beta(2)m underwent substantial changes in morphology similar to those observed when monocytes differentiate into macrophages. The cultured cells increased in size and vacuolization, and their content of beta-glucuronidase and acid phosphatase increased by 5- to 10-fold at day 4. Expression of the monocyte--macrophage membrane antigens HLA-DR, CD11b, and CD11c also increased at day 4. Although exhibiting phenotypic characteristics of macrophages, monocytes cultured with AGE-beta(2)m functioned differently than macrophages cultured with serum. Superoxide production in response to phorbol myristic acetate was maintained in monocytes cultured with AGE-beta(2)m, but declined with time in cells cultured with serum. Constitutive synthesis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) increased in monocytes cultured for four to six days with AGE-beta(2)m. CONCLUSIONS: These findings support a novel role for AGE-modified proteins such as AGE-beta(2)m that may contribute to the development of a local inflammatory response, with predominant accumulation of monocytes/macrophages, in DRA.

Antibodies↗

PubMed2005

Safe and rapid laparoscopic access--a new approach.

Despite numerous recent technical advances in minimally invasive surgical technique, the potential exists for serious morbidity during initial laparoscopic access. Safe access depends on adhering to well-recognized principles of trocar insertion, knowledge of abdominal anatomy, and recognition of hazards imposed by previous surgery. Applying these principles, we describe a safe, rapid, and cost-effective technique for laparoscopic access using readily available instruments. This technique emphasizes identification and incision of the point at which the midline abdominal fascia is fused with the base of the umbilicus, and the importance of the application of countertraction directly at the point of insertion. This method allows penetration under direct vision with minimal controlled axial force, and without the requirement for fascial sutures or other cumbersome aspects of the traditional open technique. While previous reports describe techniques for laparoscopic access entry based on similar anatomic and surgical principles, we describe an alternative method not yet discussed in the surgical literature.

Abdomen↗

PubMed2003

Basic science priorities for therapeutics research.

For more than 10 years, drug discovery efforts have concentrated on relatively few viral targets: reverse transcriptase (RT) and protease (PR). While viral load can be reduced by combining RT and PR inhibitors in regimens referred to as highly active antiretroviral therapy (HAART), recent studies suggest that many treatment failures occur because of the development of drug resistance and lack of adherence to complicated and often toxic regimens. Recently, new classes of agents directed at the virus binding and entry process have entered the development pipeline, with one such agent now approved for use in patients with HIV. Early data suggests, however, that the development of resistance will continue to be a problem as new agents are introduced into HAART regimens. With regard to the immune system, it has become clear that the damage caused by HIV infection is only partially reversed by HAART. Vaccination represents a major new immunologic approach to complement drug treatment. Thus, while advances continue to be made, there remains an urgent need for the identification of new host and viral targets, novel drugs and delivery systems, and immunologic approaches to address the dual problems of drug resistance and toxicity. To address this need, the Division of AIDS has established basic science priorities in the following areas of therapeutics research: host and viral targets, inhibitors, vaccines, innate immunity, viral reservoirs, and gene therapy.

Anti-HIV Agents↗

PubMed1992

Patient and renal allograft survival in the late posttransplant period.

Finding the proper balance between too much and not enough immunosuppression is just as important in the late posttransplant period as it is during the first year after transplantation. In general, too much immunosuppression leads to an increase in patient mortality, whereas inadequate immunosuppression can lead to an inordinately high rate of allograft failure (Fig 5). In the late posttransplant period, patient and allograft survival are both critically dependent on the degree of immunosuppression and on the long-term side effects of the agents used to achieve this immunosuppression. Adequate immunosuppression is important in treating and preventing the acute allograft rejection episodes that are common during the first year after transplantation (Fig 6). Some data suggest that the severity of early acute rejection episodes may influence the development of chronic rejection, the most common cause of graft failure in the late posttransplant period. Otherwise, the role of immunosuppression in treating and preventing chronic rejection is unclear. The discontinuation of immunosuppression by noncompliant patients is a major cause of late graft failure. Whether the nephrotoxicity of CsA will also result in graft failure in the very late posttransplant period is still unknown. The agents used to achieve immunosuppression, along with decreased graft function and proteinuria, contribute to hypercholesterolemia, hypertension, and hyperglycemia. These and other risk factors have a negative impact on both graft and patient survival. Thus, immunosuppression is directly, or indirectly linked to most of the common causes of death and graft failure after renal transplantation. Although potent new immunosuppression protocols have increased the rate of short-term patient and allograft survival after renal transplantation, future advances in long-term survival after renal transplantation will depend on improvements that are effective in the late posttransplant period. Currently, the best approach to preventing complications in the late posttransplant period is to maintain a vigilant, comprehensive program of on-going medical care. The minimal amount of immunosuppression required to prevent allograft rejection should be used, while adhering to the principle that it is better to lose the graft than to lose the patient.

Bacterial Infections↗

PubMed2006

Can evidence-based prevention programs be sustained in community practice settings? The Early Risers' Advanced-Stage Effectiveness Trial.

This study evaluated institutional sustainability of the Early Risers "Skills for Success" conduct problems prevention program. In a previous early-stage effectiveness trial Early Risers had been successfully implemented by a nonprofit community agency with guidance, supervision, technical assistance and fiscal support/oversight provided by program developers. The current advanced-stage effectiveness trial applied a randomized, control group design to determine whether this community agency could replicate earlier positive findings with a new cohort of participants, but with less direct involvement of program developers. An intent-to-intervene strategy was used to compare children randomly assigned to Early Risers or a no-intervention comparison group. Compared to results obtained in an early-stage effectiveness trial, program attendance rates were much lower and only one positive outcome was replicated. Failure to replicate program effects was not attributed to poor program implementation, because data collected pertaining to exposure, adherence and quality of delivery were acceptable, and a participation analysis showed that families who attended at higher levels did benefit. It was difficulties that the community agency experienced in engaging families in program components at recommended levels that primarily accounted for the results. Possible organizational barriers that impeded sustainability included unreliable transportation, poor collaboration between the agency and the local public school system, high staff turnover, agency downsizing, and fiduciary responsibility and accountability. It was concluded that both program developers and program providers need to be proactive in planning for sustainability.

Child↗

PubMed2004

Online recognition of Chinese characters: the state-of-the-art.

Online handwriting recognition is gaining renewed interest owing to the increase of pen computing applications and new pen input devices. The recognition of Chinese characters is different from western handwriting recognition and poses a special challenge. To provide an overview of the technical status and inspire future research, this paper reviews the advances in online Chinese character recognition (OLCCR), with emphasis on the research works from the 1990s. Compared to the research in the 1980s, the research efforts in the 1990s aimed to further relax the constraints of handwriting, namely, the adherence to standard stroke orders and stroke numbers and the restriction of recognition to isolated characters only. The target of recognition has shifted from regular script to fluent script in order to better meet the requirements of practical applications. The research works are reviewed in terms of pattern representation, character classification, learning/adaptation, and contextual processing. We compare important results and discuss possible directions of future research.

Algorithms↗

PubMed2003

Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation.

OBJECTIVES: The study evaluated a nonsurgical means of intramyocardial cell introduction using the coronary venous system for direct myocardial access and cell delivery. BACKGROUND: Direct myocardial cell repopulation has been proposed as a potential method to treat heart failure. METHODS: We harvested bone marrow from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells, labeled them with the gene for green fluorescence protein, expanded them in culture, and resuspended them in a collagen hydrogel. Working through the coronary sinus, a specialized catheter system was easily delivered to the anterior interventricular coronary vein. The composite catheter system (TransAccess) incorporates a phased-array ultrasound tip for guidance and a sheathed, extendable nitinol needle for transvascular myocardial access. A microinfusion (IntraLume) catheter was advanced through the needle, deep into remote myocardium, and the autologous cell-hydrogel suspension was injected into normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1 control/collagen biogel only), and 28 (n = 2), and the hearts were excised and examined. RESULTS: We gained widespread intramyocardial access to the anterior, lateral, septal, apical, and inferior walls from the anterior interventicular coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other procedural complications occurred. Gross inspection demonstrated no evidence of myocardial perforation, and biogel/black tissue dye was well localized to sites corresponding to fluoroscopic landmarks for delivery. Histologic analysis demonstrated needle and microcatheter tracts and accurate cell-biogel delivery. CONCLUSIONS: Percutaneous intramyocardial access is safe and feasible by a transvenous approach through the coronary venous system. The swine offers an opportunity to refine approaches used for cellular cardiomyoplasty.

Animals↗

PubMed2005

Designs in partially controlled studies: messages from a review.

The ability to evaluate effects of factors on outcomes is increasingly important for studies that control some but not all of the factors. Although important advances have been made in methods of analysis for such partially controlled studies, work on designs has been limited. To help understand why, we review the main designs that have been used for such partially controlled studies. Based on the review, we give two complementary reasons that explain the limited work on such designs, and suggest a new direction in this area.

Cluster Analysis↗

PubMed1996

Prevention of transfusion-associated cytomegalovirus infection. Practice parameter. American Society of Clinical Pathologists.

This practice guideline represents the opinions and recommendations of the author(s), the American Society of Clinical Pathologists (ASCP) Practice Parameters Committee and the ASCP Board of Directors regarding the appropriate strategies for each clinical condition or laboratory test discussed in this guideline. This guideline is designed primarily as an educational resource for physicians in the provision of quality medical services. Adherence to this guideline is completely voluntary and does not necessarily assure a successful medical treatment or result. This practice guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures or tests that are reasonably directed to obtaining the same results. The physician should apply his or her own professional judgment to the unique clinical circumstances presented by the particular procedure or test. Physicians are encouraged to document the reasons for whatever procedure or test they use (whether or not in conformance with this guideline). Physicians should also take care to consider other medical and scientific advances that are available after the date of adoption of this guideline. This practice guideline was developed exclusively for the purposes set forth above and not for use in connection with matters involving reimbursement, credentialing, or utilization review.

Adult↗

PubMed1997

Role of physiological conditions in the oropharynx on the adherence of respiratory bacterial isolates to endotracheal tube poly(vinyl chloride).

Pneumonia is a major problem in intensive care patients and can be induced by pathogenic bacteria adhering to poly(vinyl chloride) (PVC) endotracheal (ET) tubes. This study examines the influence of surface properties on the adherence of the respiratory isolates Staphylococcus aureus and Pseudomonas aeruginosa to PVC. In particular, the influence of respiratory tract physiological conditions, 5% CO2 and saliva, on adherence was investigated. In general, decreased adherence to PVC was observed when bacteria were grown in CO2. When these CO2-grown bacteria were treated with saliva their adherence to PVC significantly increased; however, their adherence was significantly reduced to saliva-treated PVC. Treatment of both bacterial isolates with saliva decreased their negative zeta potential, a factor which may directly contribute to the observed increased microbial (saliva pretreated) adherence to PVC. Cell surface hydrophobicity (CSH) was evaluated by measuring the initial rates of microbial removal from a buffered aqueous phase, to ensure the absence of electrostatic interactions, to an organic phase (xylene). Under physiological conditions, CSH did not appear to be a dominant factor in biomaterial adherence as the CSH of S. aureus was decreased by saliva treatment but was unchanged for Ps. aeruginosa. Additionally, CSH also differed for the two isolates when grown in CO2, significantly decreasing with S. aureus but remaining unaltered with Ps. aeruginosa. Saliva treatment of PVC also decreased the advancing and receding contact angles of the biomaterial and its surface roughness, which may be a factor in the decreased adherence of saliva-treated bacteria to this surface. Alternative biomaterials or surface modifications appear necessary for the desired improvements in ET tube effectiveness. This study highlights the influence of physiological conditions on biomaterial and bacterial surface characteristics and subsequent interactions. It is imperative that the physiological conditions predominating in the clinical area of biomaterial use be considered when investigating device biocompatibility.

Bacterial Adhesion↗

PubMed2001

Update on HIV/AIDS in Thailand.

Thailand experienced its first case of AIDS in 1984. Approximately 800,000 Thais were infected with HIV in 1995 and 1 million Thais became infected by the year 2000. There have been 5 major epidemic waves: among male homosexuals (started 1984-5), intravenous drug users (started 1988), female commercial sex workers (started 1989), male clients (started 1990), and housewives and the newborn (started 1991). Approximately 96 per cent of HIV-1 infected Thais carried recombinant subtype A/E, the rest carried B'. In a male seroconvertors cohort of 235 cases, median time to show CD4 <200 cells/microL was 6.8 years. Five years survival was significantly lower than that of the other subtype B seroconvertors study, i.e., 82 per cent compared to 90 per cent. Interestingly, 13.5 per cent of seronegative Thais showed homozygous SDF1-3'A polymorphism, which suggests that approximately one-tenth of Thais may become long-term non-progressors after HIV-1 infection. Primary HIV infection syndrome is rare among Thai patients (1.1%). In contrast, it was 50-90 per cent in Western cohorts. In early symptomatic patients, one-third developed pruritic pappular eruptions (PPEs). In advanced stage, disseminated tuberculosis, Pneumocystis carinii pneumonia (PCP), cryptococcosis, and esophageal candidiasis are commonly found. In Northern Thailand, however, Penicillium marneffei infection or penicillosis is more common than cryptococcosis. The recent understanding of HIV pathogenesis suggests that HIV eradication is unlikely to be achievable with current strategies. Several National HIV treatment guidelines including the Thai guideline have been recommended treatment with triple antiretroviral regimen when patients become symptomatics or CD4+ <200. Current development of antiretroviral therapy which includes new agents, new formulas, and pharmacokinetic enhancements, is directed to better potency, higher genetic resistant barrier, less pill burden, and once a day dosing. These will ultimately improve the adherence and the long-term effectiveness of antiretroviral treatment. In reality, however, although the cost of triple regimen is dramatically declining, many patients still can not afford it. Primary prophylaxis and early diagnosis and treatment of opportunistic infection should be considered in patients with CD4+ <200 cells/microL. Modified short course ZDV studies and donation campaigns for preventing mother-to-child transmission, clinical trials to investigate the best use of expensive anti HIV medications in a poor resource setting have been or are being conducted. Nine phase I/II HIV-1 vaccine trial protocols have been or are being tested. A phase III trial of gp120 subtype B/E (AIDSVAX, VaxGen) was started in 1999, a total of 2,500 volunteers will be enrolled, and interim analysis is planned for August 2002. Thai investigators are also participating in pre-clinical development of recombinant BCG and DNA vaccines. Multidisciplinary and multi-level approaches, both by the government and private sectors, have had a positive impact on the HIV epidemic as shown by the declining seroprevalence of HIV infection in Thai male conscripts, and of major sexually transmitted diseases in men. Nevertheless, more effort at the grass roots level is needed to ensure further success and sustainability of the control of the HIV epidemic in Thailand.

AIDS-Related Opportunistic Infections↗