Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether patient and hospital characteristics were significantly associated with variations in Pneumocystis carinii (PCP) care and outcomes, we analyzed the use of diagnostic tests, intensive care units (ICUs), anti-PCP medications for persons hospitalized with human immunodeficiency virus (HIV)-related PCP, and hospital discharge status. We conducted retrospective chart reviews of a cohort of 2,174 patients with PCP hospitalized in 1987-1990. Outcomes included process of care for PCP and in-hospital mortality rates. Persons with PCP who were more severely ill at admission were more likely to have early medical care, to receive care in an intensive care unit, and to die in hospital. After we adjusted for differences in this severity of illness, we noted that Medicaid patients, injection drug users (IDUs), and patients treated at VA or county hospitals were significantly less likely than others to have diagnostic bronchoscopies and that persons covered by Medicaid, with a previous diagnosis of acquired immunodeficiency syndrome (AIDS), who did not receive prior zidovudine (AZT) or who received care in a VA hospital had the highest chances of in-hospital death. Insurance and risk group characteristics, severity of illness, and hospital characteristics appear to be the most important determinants of the intensity and timing of medical care and outcomes among patients hospitalized with PCP.
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PMID:Predictors of resource utilization for hospitalized patients with Pneumocystis carinii pneumonia (PCP): a summary of effects from the multi-city study of quality of PCP care. 867 47

From last years eighty's decade the number of women with HIV infection have significantly increased. To know the epidemiological and clinic trades in this group we studied retrospectively 476 HIV infected patients attending in a General Hospital from January 1986 to June 1993. Seventy nine (16.5%) were female and 397 male. The mean female group was 25.8 years, 61.9% were IVDUs and 30.4% heterosexual transmission. This last transmission route was more important between females than males (5%) (p < 0.001) and in 1992 the 55% of women been infected by this way. The mean CD4 count was 643 cel/ml in the female group at the diagnostic time and 21.7% developed antigenaemia without difference with the male group. 59.7% of women were no symptoms at the diagnosis time and 14.3% were AIDS, no differences with men, but more in the female group developed AIDS along following time 39.5% in front of 24.7% in the male group (p < 0.05). Disseminated Tuberculosis (DTB) (29.1%) and Wasting Syndrome (WS) (29.1%) were the more frecuent AIDS defining conditions in the female group. The more frecuent complications were: Oropharynx Candidiasis 39.1%, Esophagus Candidiasis 6.3%, WS 11%, DTB 12.65%, PCP 10.12% and Neoplasias 5.06%. Fourteen women became pregnant during HIV infection, no clinical nor immunological differences were observed in this group with the control. The treatment (66%) and following (46.8%), compliance was better between women than men. The rise of women with HIV infection, the poor development in this group described by some authors, so far gynecological aspect and vertical transmission makes HIV infection in women an major health problem.
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PMID:[Human immunodeficiency virus infection in women]. 867 99

This review summarises mutagenesis-related research on the major classes of DNA minor groove binding ligands. These compounds can bind to DNA covalently or non-covalently, and span a range of DNA sequence selectivities. Many of the non-covalent binders show effects on topoisomerase enzymes in mammalian cells, with the bisbenzimidazoles being the most active. Mutagenic effects consistent with topoisomerase inhibition are observed in vitro. Many of these compounds induce aneuploidy and polyploidy, properties which may also contribute to carcinogenic processes. Similarly, uvrA trapping by some minor groove binders may alter mutagenetic processes by inhibiting efficient repair. Distamycin has been shown to enhance the mutagenicity of ethidium bromide in bacteria by an undetermined mechanism. However, the inhibitory effects of minor groove binders on human DNA repair systems have not yet been reported. Hoechst 33258 and distamycin cause chromosome decondensation in both mouse and human cells particularly at heterochromatic regions which are rich in AT content. Various minor groove binders have been shown to induce fragile sites in cultured lymphocytes from susceptible individuals, which may have a propensity to develop particular cancers. Investigation of the relationship between fragile site inducing drugs and chromosomal rearrangements in fragile site carriers has not been investigated but may yield interesting results. Some DNA alkylating minor groove binders can generate lesions extremely toxic to mammalian cells (e.g., CC-1065 and analogues), and induce a range of DNA sequence changes in vivo, both at the site of covalent bonding as well as at surrounding sequences. This may be typical of alkylating minor groove binders which have a binding site size of several base pairs, and which stabilise helical structure. Minor groove binders have effects on gene expression in vitro by inhibiting the sequence selective binding of various transcription factors to DNA. These effects may result in expression or repression of downstream genes also. This class of ligand thus offers the possibility of mutations targeted to specific genes or genomic regions. It will be interesting to determine whether such examples of targeted mutagenesis, as has already been observed with CC-1065 and adozelesin, will result in an enhanced or in a lowered capacity to promote neoplastic disease. However it should be noted that pentamidine, a minor groove binder used in the treatment of AIDS-related PCP, has thus far shown no mutagenic effects in nuclear DNA and only a weak effect in mitochondrial DNA of yeast. These results suggest that minor groove binding does not necessarily lead to mutagenesis.
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PMID:The mutagenic properties of DNA minor-groove binding ligands. 878 82

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.
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PMID:AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group. 879 89

Pneumocystis carinii is a common cause of pneumonia in individuals who are immunosuppressed by HIV infection. Use of molecular biological techniques show that P. carinii is a fungus and that infection in man is not a zoonosis. Invasive tests such as sputum induction or bronchoscopy are used to make the diagnosis of P. carinii pneumonia. Life long primary prophylaxis is given to HIV positive individuals with CD4+ lymphocyte counts < 0.20 x 10(9)/L or a CD4: total lymphocyte ratio of < 1.5, constitutional symptoms, or with other AIDS defining diseases. Secondary prophylaxis is given after a first episode to prevent a recurrence. First choice for primary and secondary prophylaxis is oral co-trimoxazole 960 mg od or three times a week. In patients who are intolerant to co-trimoxazole, nebulised pentamidine or dapsone (with or without pyrimethamine) are second and third choices. In a patient with acute PCP disease, severity should be assessed using clinical, radiographic and blood gas criteria as those with moderate or severe disease will benefit from adjuvant glucocorticoids. Co-trimoxazole (120 mg/kg/day in divided doses for 21 days) is first choice therapy for PCP of all degrees of severity. In patients who fail to respond to co-trimoxazole or who are intolerant to it, second line treatment is iv pentamidine in those with severe disease and oral dapsone with trimethoprim, oral clindamycin with primaquine or iv pentamidine in those with mild or moderately severe disease.
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PMID:Pneumocystis carinii infection: current treatment and prevention. 881 28

Although alternative therapy for PCP remains limited, the role of TMP/SMX desensitization becomes increasingly important in patients with AIDS. Various successful desensitization protocols have been described in this article. As there are no established guidelines, it appears that the desensitization procedure can occur in small successive doses given each day or one small dose given daily. An evaluation of the severity of allergic reaction can be used to determine the type of dosing regimen. We believe that protocols starting with low doses and slow titration to full-dose therapy, as used at our institution, should be efficacious. Monitoring of the patient after the desensitization procedure should continue, as sensitivity may reoccur. In addition, while the patient is undergoing desensitization, some investigators recommend that alternative therapy be continued until full-dose TMP/SMX therapy is achieved. Also, it is important to realize that once a patient is successfully desensitized, medication compliance must be maintained because, theoretically, reexposure to the drug after a lapse in therapy may result in hypersensitivity reactions. Therefore, this procedure and the possibility of serious adverse effects, such as Stevens-Johnson syndrome and anaphylaxis, should be evaluated carefully and discussed thoroughly with each patient prior to initiation of therapy. Finally, a study of sufficient size should be performed to evaluate the efficacy of desensitization regimens and establish specific dosing guidelines.
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PMID:Trimethoprim/sulfamethoxazole desensitization. 883 54

The opportunistic infections, malignancies, and causes of death related to acquired immunodeficiency syndrome (AIDS) are changing, perhaps as a result of improved treatment, prophylaxis, and education. With its high percentage of persons who acquired the human immunodeficiency virus from intravenous drug (IVD) use, the population of patients with AIDS in the Bronx is potentially unique. All of the 257 consecutive adult human immunodeficiency virus and/or AIDS cases from two Bronx teaching hospitals from 1982 through 1995 were collected. The reports were reviewed for patient demographics, opportunistic infections, malignancies, and causes of death. One hundred thirteen cases from 1982 through 1988 were compared with 144 cases from 1989 through 1995, separated by the institution of antiretroviral therapy and Pneumocystis carinii (PCP) prophylaxis in the latter period. Male homosexuality as a risk factor significantly decreased from 24.8% of the cases in our study from the 1982/88 period to 12.5% during the 1989/95 period (P = 0.014), but IVD use cases showed no change. Cases of AIDS in heterosexual patients increased from 23.9 to 36.1% (P = 0.041) but did not achieve statistical significance unless the unknown risk category (a population shown to be infected predominantly through heterosexual transmission) was included. The prevalence of PCP at autopsy as an opportunistic infection decreased from 37.2 to 25% (P = 0.04), and its prevalence as a cause of death decreased from 31.9 to 13.9% (P = 0.007). This decrease was seen in the homosexual and heterosexual populations but not in the population of IVD users. The homosexual population, as opposed to the population of IVD users, may have taken greater advantage of PCP treatment and prevention. As a result, bronchopneumonia, not PCP, is now the leading cause of death among the patients with AIDS in this study. These findings have important implications for therapy and prophylaxis to control the spread of AIDS and its related infections, particularly in an inner city population troubled by drug use and poverty.
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PMID:Comparison of changing autopsy trends in the Bronx population with acquired immunodeficiency syndrome. 890 38

Many clinical trials follow patients for several different types of survival endpoints, such as mortality, disease progression, and time until dose-limiting toxicity. Conduct of such trials often requires that the accumulating data be reviewed periodically to protect the safety of participating patients and possibly identify early treatment differences. This paper proposes a group sequential method for assessing multiple survival endpoints using repeated confidence intervals. Counting processes for each survival endpoint are used to estimate both the correlation between outcomes and between times of interim analysis. The methods are illustrated using a clinical trial comparing two treatments for PCP prevention in AIDS patients. The operating characteristics of three strategies for constructing confidence intervals are assessed and compared in a simulation study.
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PMID:Sequential monitoring of clinical trials with multiple survival endpoints. 893 Dec 5

The problem of drug abuse in America encompasses all ages, economic, and ethnic groups. The Office of the Chief Medical Examiner (OCME) has recorded a continuous increase in drug abuse deaths in Maryland over the past seven years. This report focuses on the epidemiological characteristics and pathological findings of victims of fatal drug abuse in Maryland investigated by the OCME in 1992 and 1993. A retrospective study of OCME cases in 1992 and 1993 yielded a total of 605 deaths caused by drugs of abuse. 426 deaths were the result of narcotic drug use, 66 deaths due to cocaine, 102 deaths involved both narcotics and cocaine, 6 deaths were due to phencyclidine (PCP) and 5 involved both PCP and narcotic drugs. Drug abuse deaths most often involved individuals who were male (86%) and black (64%). Their ages ranged from 15 to 68 years with the majority (58%) of victims being in their 30's. Of the 605 drug deaths, 393 (65%) had a known history of drug abuse. 279 (46%) exhibited needle tracks, of which only 94 (16%) had identifiable fresh needle puncture marks. Drug paraphernalia (needles, syringes, etc.) was found at the scene in 22% of the cases. Twenty-nine (4.8%) cases showed complications of drug abuse which included pneumonia, endocarditis or myocarditis, pulmonary embolism, AIDS and intracerebral hemorrhage. 87 (14.4%) were positive for HIV antibodies, an incidence much higher than that identified in our general autopsy population (2.6%). Drugs of abuse were also found in a significant portion of the homicides examined at this office in 1992 and 1993. 323 of the 1265 homicide victims (25%) showed evidence of some form of illicit drug activity.
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PMID:Observations on drug abuse deaths in the State of Maryland. 893 5

Because of their often profound immune suppression, persons with HIV-infection are, increasingly, being identified as having morbidity related to mycobacteria. Indeed, mycobacterial disease is now the second most frequent cause of illness in AIDS patients receiving PCP prophylaxis with the majority of these patients in the United States having disease caused by M. avium complex (MAC). This section reviews the epidemiology, clinical presentation, treatment protocols, and prophylaxis strategies for MAC, as well as the other species of nontuberculosis mycobacteria being diagnosed in the setting of HIV infection. These organisms typically cause extrapulmonary, often disseminated disease in HIV infected persons, although pulmonary disease may occur. The prompt diagnosis and successful treatment of these infections can prolong the life and enhance its quality for affected patients with HIV coinfections.
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PMID:Nontuberculous mycobacteria in patients with human immunodeficiency virus infection. 897 82


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