Gene/Protein Disease Symptom Drug Enzyme Compound
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Topical and systemic steroids have proven to be invaluable agents in the treatment of a wide range of disorders, but their use is not without potential complications. Before initiation of therapy with systemic steroids, a personal or family history of cataracts, glaucoma, hypertension, diabetes, hyperlipidemia, renal stones, peptic ulceration, and current infection or pregnancy should be ascertained, because these patients have an increased risk of complications. Prior to long-term therapy with systemic steroids, blood pressure measurement, tuberculin skin test, and anergy panel are recommended. Monthly follow-up may include measurements of weight, blood pressure, electrolytes, and blood sugar and guaiac testing of the stool. To prevent the ocular complications of steroid therapy, routine screening is indicated (Table 1). Screening for cataracts, which occur most commonly as a sequela of continuous systemic steroid use, may be performed by slit-lamp examinations conducted three or four times a year for patients on long-term therapy and twice a year for patients taking intermittent topical ocular or systemic steroids. Glaucoma is more often associated with topical ocular or periocular steroids than with systemic steroids; recommended screening includes a baseline intraocular pressure measurement, then routine pressure measurements taken every few weeks initially, then every few months. Ocular rebound inflammation may develop secondary to rapid tapering or abrupt discontinuation of topical ocular steroid use and is best prevented with gradual tapering. Opportunistic infections of the eye include bacterial, viral, and fungal infections and are most often associated with the use of topical ocular steroids. Ophthalmologic evaluation is indicated promptly if patients treated with ocular steroids develop ocular discharge, pain, photophobia, or redness.
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PMID:Ocular effects of topical and systemic steroids. 161 9

This descriptive study investigated quality of life issues, biochemical indices, and nutritional parameters of individuals with HIV/AIDS before the initiation of protease inhibitors (PI) and after PI therapy. Telephone interviews were conducted with 45 men and women who were diagnosed with HIV/AIDS. A 26-item subjective questionnaire was used to determine intake of liquid nutritional supplements, use of micronutrient and herb supplements, adherence to modified diets, gastrointestinal symptoms, employment status, sociability, and ability to conduct activities of daily living. A medical chart review was conducted to collect data on biochemical indices, weight, medication regimens, and incidence of opportunistic infections. The results of the study suggest that HIV/AIDS individuals gain weight, improve CD4 counts, and decrease HIV RNA viral load while on PI-based drug combination therapy. Opportunistic infections decreased, quality of life was improved, and blood albumin was elevated. Hyperlipidemia, that is, elevations in total cholesterol and triglycerides, was observed in study participants (44% and 40% of patients, respectively) after PI therapy. These findings support the need for future investigations to examine the long-term influence of PI-based combination drug therapies on nutrient intake, body composition, and quality of life of persons with HIV/AIDS.
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PMID:Perception of quality of life of persons with HIV/AIDS and maintenance of nutritional parameters while on protease inhibitors. 1087 May 96

Recommendations for a highly active antiretroviral therapy (HAART) in either pretreated patients or symptomatic patients with an AIDS-defining event are based on a combination of three or more agents from different antiretroviral classes including two nucleoside reverse transcriptase inhibitors with at least one protease inhibitor. The majority of currently available protease inhibitors are coadministered with low-dose ritonavir as a pharmacoenhancer that significantly increases protease inhibitor plasma concentrations. Atazanavir is a highly active azapeptide inhibitor of the HIV protease. It was the first, and to date the only, protease inhibitor designed to be applied once daily (q.d.) and is expected to overcome the problems of earlier agents of this class of drugs, such as unfavorable adverse events like hyperlipidemia, diarrhea and lipodystrophy. Atazanavir, formerly known as BMS-232632, can be dosed either at 400 mg q.d. without a pharmacoenhancer as first-line HIV therapy or combined with ritonavir as atazanavir/ritonavir 300/100 mg q.d. for therapy-experienced patients. The pharmacoenhancing effect of ritonavir on atazanavir resulted in a potent, clinically effective and well-tolerated antiretroviral drug with high plasma concentrations and a sufficient genetic barrier to viral resistance. Nevertheless, noninferiority to lopinavir/ritonavir-containing HAART could not be shown when atazanavir was given unboosted in pretreated patients in the AI424-043 study. When atazanavir was boosted with low-dose ritonavir its efficacy was comparable to that of lopinavir/ritonavir in non-naive patients (AI424-045 study). Additionally, specific side effects were identified during clinical practice, such as an increased rate of patients with jaundice, and, more recently, genetic risk factors causing hyperbilirubinemia. Atazanavir inhibits glucuronyltransferase, an enzyme responsible for the metabolism of bilirubin in liver, thus increasing unconjugated bilirubin levels in blood. However, atazanavir itself also enhances plasma concentrations of other coadministered HIV-1 protease inhibitors, so that its use as a combination partner in boosted double protease inhibitor combinations, with or without the addition of nucleoside reverse transcriptase inhibitors, is being evaluated. Unboosted atazanavir is approved for first-line HIV therapy in adults in the United States, and atazanavir/ritonavir is recommended for the second-line therapy of HIV-1 infection in adult HIV-1-infected patients in the United States and the European Union. More recently, data from the CASTLE study (AI424-138) have been reported at the 15th Conference on Retroviruses and Opportunistic Infections by Molina et al., where boosted atazanavir-containing HAART was compared to a regimen with lopinavir/ritonavir in therapy-naive patients.
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PMID:Atazanavir/ritonavir: a review of its use in HIV therapy. 1838 89

HIV/AIDS is still an important health problem worldwide and the number of people living with HIV worldwide continued to grow in the last years. The first HIV/AIDS cases had been reported in 1985 from Turkey and with an increasing trend during the following years, the number of cases reached to 3898 with 528 new cases in 2009. The aim of this retrospective study was to share the 18 years experience with the patients who were followed-up in Erciyes University Hospital Infectious Diseases Clinics in Cappadocia region. The records of 55 (81%) HIV/AIDS patients out of 68 who were admitted to our clinic between 1992- 2009 have been attained and the demographic and clinical characteristics, administered therapy regimens and adverse effects of antiretroviral therapy of those cases have been evaluated. Forty-three (78%) of the patients were male and 12 (22%) were female of which 11 (92%) of their spouses had HIV/AIDS. The median age of the patients was 45 and 20 (36%) of them were over 54 years old. Fifty (91%) of patients lived in Cappadocia region, and 24 (44%) had lived in foreign countries. Fifty (91%) patients had risky heterosexual contact as a risk factor. Of these patients, 47 (85%) were in full-blown AIDS stage at admission. Twenty-seven (49%) of the patients diagnosed occasionally during routine anti-HIV testing, did not have any symptoms. Fever, weakness and weight loss were the most frequently detected symptoms in the rest of the patients. Ten (18%) patients had underlying diseases such as hypertension, chronic hepatitis B or C, coronary artery disease, diabetes mellitus and chronic renal disfunction. Opportunistic infections were determined in 25 (45.5%) patients and 20 (40%) of these infections were determined at admission. The most frequent opportunistic infection was oral candidiasis, followed by Pneumocystis (carinii) jiroveci pneumonia and tuberculosis. Malignancy was diagnosed in three patients; two had Kaposi's sarcoma and one had multiorgan adenocarcinoma. Antiretroviral therapy was started in 37 (67%) of the patients and lamivudin/zidovudin + lopinavir/ritonavir was the most commonly used combination. Antiretroviral therapy was changed in 13 (35%) patients most frequently due to the development of side effects of the drugs. Nausea, vomiting and hyperlipidemia were the most frequent side effects, while diarrhea, skin rashes, anemia, leucopenia and lipoatrophy have also been detected. One patient discontinued therapy by his own will. Sixteen (27.6%) of 58 patients, whose records could be achieved, died. The mortality rates detected in 1992-1999 and 2000-2009 periods were 78.6% (11/14) and 11.4% (5/44), respectively. The mean exitus time of the patients was six months after the diagnosis. The reasons of mortality were opportunistic infections in six patients, and adenocarcinoma in one patient. Autopsy had been performed in seven cases, however three patients' records could be attained. One had disseminated candidiasis and miliary tuberculosis, one had multiorgan carcinoma, and one had pneumonia, kidney and colon necrosis and condyloma acuminata. In conclusion, increasing awareness of physicians about HIV/AIDS epidemiology in Turkey provides early diagnosis and prevents the dissemination of illness in community.
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PMID:[Epidemiological and clinical characteristics of HIV/AIDS patients followed-up in Cappadocia region: 18 years experience]. 2134 Nov 67

Advances in immunosuppressants for solid organ transplantation (SOT) have improved prevention and treatment of acute rejection as well as reduced the risk of chronic graft damage. However, SOT recipients are prone to developing opportunistic infections because of their long-term immunosuppressed status. Tuberculosis (TB) is a serious opportunistic infection that is associated with increased morbidity and mortality in SOT recipients. However, nationwide population-based research specifically focused on the associations between kidney transplantation (KTx), liver transplantation (LTx), and heart transplantation (HTx), and subsequent TB infection is lacking. This study was conducted using Taiwan's National Health Insurance Research Database, which provided claims data for SOT recipients from 2000 to 2009. Clinical features, treatment, and outcomes were analyzed to determine the risk for TB after SOT. In total, 153 (3.2%) RTx, 19 (1.1%) LTx, and 26 (2.8%) HTx recipients became infected with TB. Compared with non-TB patients, HTx recipients with TB had significantly higher prevalence of older age (P = .037), hypertension (P < .001), and coronary artery disease (CAD) (P = .002). There were also greater percentages of male sex (P = .018), diabetes (P = .029), hyperlipidemia (P = .016), CAD (P < .001), and chronic obstructive pulmonary disease (COPD) (P < .001) in RTx recipients with TB than in those without. In conclusion, posttransplantation TB is a serious problem worldwide, and a high index of suspicion is warranted to ensure early diagnosis and prompt initiation of treatment for TB among SOT patients. In this preliminary study, KTx recipients had a higher risk of TB infection than LTx and HTx recipients, and the high-risk factors were male sex, diabetes, hyperlipidemia, CAD, and COPD. The use of optimal immunosuppressive agents to minimize acute rejection, monitoring of high-risk recipients, prompt diagnosis, and appropriate treatment are required for the management of TB infection in endemic areas such as Taiwan.
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PMID:A nationwide population-based study of the risk of tuberculosis in different solid organ transplantations in Taiwan. 2481 20