Discontinuation of secondary prophylaxis in patients with cytomegalovirus retinitis who have responded to highly active antiretroviral therapy.
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We performed a prospective study of discontinuation of secondary prophylaxis against cytomegalovirus (CMV) in 36 patients with acquired immunodeficiency syndrome and quiescent CMV retinitis after successful treatment with highly active antiretroviral therapy (HAART). No reactivation or progression of retinitis was observed in 35 patients with persistent response to HAART, findings that support the discontinuation of secondary prophylaxis against CMV retinitis in such patients. (+info)
Angiogenesis in oral cancer.
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Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that develops after years of chronic exposure to alcohol and tobacco products. Exposure to these agents results in alterations of genes that are important in the regulation of various cellular functions. This loss of regulation allows the tumor cells to survive and grow in an unchecked manner by allowing the cells to perform functions that contribute to the growth of the tumor. Some of these important changes include the acquisition of immortality and the ability to invade tissue and/or metastasize to other sights, as well as acquiring the ability to induce angiogenesis. Angiogenesis, the growth of new blood vessels from pre-existing ones, is a complex phenomenon that is absolutely required for the continued growth and survival of solid neoplasms. Without new blood vessels to provide nutrients and remove waste, tumors would be unable to grow larger than 2-3 mm in diameter. Therefore, one could envision its potential role in both the treatment and prevention of malignancies such as HNSCC. The concept of chemoprevention is extremely important in HNSCC since patients often develop multiple independent lesions throughout the mucosa of the upper aerodigestive tract. Therefore, the comprehensive treatment of this disease must address not only the initial primary neoplasm, but also prevent the progression of the premalignant lesions lurking throughout the rest of the mucosal surfaces. This review will outline the basic changes that occur in tumor cells that result in the switch to angiogenic phenotype. In addition, it will discuss the present status of using antiangiogenic agents in the treatment of cancer. Finally, this paper will present a rationale for the use of multiple antiangiogenic agents as a means of developing new chemotherapeutic and chemopreventive protocols that may result in reduced patient toxicity while maintaining similar clinical efficacies. (+info)
Perspectives on antiviral use during pandemic influenza.
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Antiviral agents could potentially play a major role in the initial response to pandemic influenza, particularly with the likelihood that an effective vaccine is unavailable, by reducing morbidity and mortality. The M2 inhibitors are partially effective for chemoprophylaxis of pandemic influenza and evidence from studies of interpandemic influenza indicate that the neuraminidase inhibitors would be effective in prevention. In addition to the symptom benefit observed with M2 inhibitor treatment, early therapeutic use of neuraminidase inhibitors has been shown to reduce the risk of lower respiratory complications. Clinical pharmacology and adverse drug effect profiles indicate that the neuraminidase inhibitors and rimantadine are preferable to amantadine with regard to the need for individual prescribing and tolerance monitoring. Transmission of drug-resistant virus could substantially limit the effectiveness of M2 inhibitors and the possibility exists for primary M2 inhibitor resistance in a pandemic strain. The frequency of resistance emergence is lower with neuraminidase inhibitors and mathematical modelling studies indicate that the reduced transmissibility of drug-resistant virus observed with neuraminidase inhibitor-resistant variants would lead to negligible community spread of such variants. Thus, there are antiviral drugs currently available that hold considerable promise for response to pandemic influenza before a vaccine is available, although considerable work remains in realizing this potential. Markedly increasing the quantity of available antiviral agents through mechanisms such as stockpiling, educating health care providers and the public and developing effective means of rapid distribution to those in need are essential in developing an effective response, but remain currently unresolved problems. (+info)
Zanamivir: from drug design to the clinic.
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The development of the neuraminidase inhibitors has revolutionized the management options for influenza. Zanamivir was the first such inhibitor to be approved for the treatment of influenza in humans. It is delivered by inhalation to the respiratory tract, which is the site of viral replication, in order to ensure immediate antiviral activity. Early treatment with zanamivir in clinical trials rapidly reduced the severity and duration of influenza symptoms and associated complications. Furthermore, chemoprophylaxis with zanamivir was shown to be effective in the prevention of influenza illness. To date, there is no evidence for the emergence of clinically significant zanamivir-resistant isolates. In conclusion, zanamivir offers a useful complementary strategy to vaccination in the effective management of influenza. (+info)
Influenza diagnosis and treatment: a view from clinical practice.
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Influenza is a descriptive term for respiratory epidemic disease presenting with cough and fever. Influenza viruses are probably the most important of the pathogens that cause this condition. Clinical influenza occurs almost every winter in England and Wales and the outbreaks last 8-10 weeks. In recent years, influenza B virus outbreaks have occurred in January and February, whereas influenza H3N2 virus outbreaks have generally started long before Christmas. Influenza H3N2 virus outbreaks pressurize health service resources in winter more than influenza B viruses, that do not have the same impact in elderly people. Infections with influenza H1N1 viruses are also usually less severe in their impact than those with influenza H3N2 viruses, but, unlike influenza B viruses, influenza H1N1 viruses have a pandemic potential along with influenza H3N2 viruses. A diagnosis of respiratory infection in primary care is based on the presenting symptoms set within the context of the current pattern of consultations of patients with similar illness. Measurement of temperature, inspection of the throat and examination of the chest or ears add a little to the diagnostic process, but in general these procedures do not help in identifying the organism. However, if it is known that influenza viruses are circulating in the community, the probability of influenza as the cause is greatly increased, as was shown in clinical trials of neuraminidase antivirals. Maximum confusion occurs when respiratory syncytial virus (RSV) and influenza cocirculate. Although RSV infection can occur throughout the winter in young children, it assumes more of an epidemic character just before Christmas in children and possibly in adults just after. During seven of the last 20 winters, influenza has been prevalent around Christmas/New Year. In routine virological surveillance of influenza-like illness in the community during the winters of 1997, 1998 and 1999, ca. 30% of swab specimens yielded influenza viruses and 20% RSV. Given the limitations for routine surveillance, including variations in the interval between illness onset and specimen capture, the quality of swab, delays in transport, the growth properties of virus culture methods, etc., these figures probably underestimate the impact of both viruses in the community. The impact of influenza is considered against the background of total respiratory infections presenting to general practitioners over the last 10 years and some comparisons are made with the 1969 pandemic experience. Lessons relevant to pandemic planning are drawn. Current options for investigation and treatment are compared with those available in 1969. These include near-patient tests for assisting with diagnosis, widespread use of vaccination as a preventive in patients at increased risk, the availability of amantadine and the newer neuraminidase inhibitor antivirals and changes in the delivery of health care. Major advances in the understanding of influenza and improvements in investigation and treatment have taken place over the last 30 years. However, there are many obstacles before these can be translated into effective management of influenza sufferers and control of major epidemics. (+info)
Impact of trimethoprim-sulfamethoxazole prophylaxis on etiology and susceptibilities of pathogens causing human immunodeficiency virus-associated bacteremia.
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The impact of chronic prophylactic administration of trimethoprim-sulfamethoxazole (SXT) on the ecology and the antimicrobial susceptibilities of bloodstream pathogens in human immunodeficiency virus (HIV)-infected patients was studied using a retrospective chart review. Eighty-nine patients with advanced HIV infection developed 124 episodes of bacteremia with 156 pathogenic isolates. Staphylococcus aureus and Enterobacteriaceae tended to be less common among patients receiving SXT. Isolates from patients receiving SXT were likelier (75%) to be resistant to 20 microg of SXT/ml than those from patients not receiving SXT (33%) (P < 0.001). (+info)
Prevention of malaria in children.
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Although malaria kills approximately 1 million children each year, preventive measures can be effective in limiting the mortality and morbidity associated with malaria. Mosquito bites can be avoided by use of appropriate environmental control and use of protective clothing, bed nets, repellents, and insecticide. Chemoprophylaxis is a mainstay of malaria prevention, and new, effective agents are increasingly available. Rapid, accurate diagnosis and effective medical treatment can help people who become ill with malaria despite their preventive efforts. With careful attention to preventive efforts, malaria should be extremely rare in travelers; similarly, broader implementation of preventive measures could decrease the burden of malaria on residents in areas where it is endemic. (+info)
Discontinuation of secondary prophylaxis against disseminated Mycobacterium avium complex infection and toxoplasmic encephalitis.
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We retrospectively studied outcomes for patients infected with human immunodeficiency virus who received highly active antiretroviral therapy (HAART) and had stopped receiving secondary prophylaxis against toxoplasmic encephalitis (TE) or disseminated Mycobacterium avium complex (MAC) infection. Nineteen patients had a history of TE, and 26 had a history of disseminated MAC infection. The median duration of secondary prophylaxis was 27 months, and the median duration of HAART before discontinuation of secondary prophylaxis was 22 months. Median CD4(+) cell counts at the time of cessation of secondary prophylaxis against TE or disseminated MAC infection were 404 and 105 cells/mm(3), respectively. Plasma virus load was undetectable in 68% of the patients who had a history of TE and in 31% of patients who had a history of disseminated MAC infection. Patients were followed up for a median of 29 months after discontinuation of secondary prophylaxis; no relapses occurred in patients with a history of TE, and 3 relapses occurred in patients with a history of disseminated MAC infection (incidence, 4 relapses per 100 person-years). (+info)