Fatal toxic epidermolysis induced by zidovudine.
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Biomedical subjects
Publications and source records attributed to R Murri.
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Detection and quantification of different Pneumocystis carinii (PC) life cycle forms were performed by polymerase chain reaction (PCR) and by morphological stains on bronchoalveolar lavage fluids (BALF) from HIV-infected patients with P. carinii pneumonia (PCP). The number of PC trophozoites was higher in patients with PCP who were receiving prophylaxis than in those not receiving prophylaxis. Also the cyst: trophozoite ratio was lower in the first group. No difference was observed between patients receiving different prophylactic medications. The imbalance between PC forms in BALF from patients with PCP receiving anti-PC prophylaxis may hamper the sensitivity of cyst stains. Multiple stains or PCR examination should be performed on BALF from patients with clinically suspected PCP who are receiving prophylaxis.
To evaluate whether the detection of Toxoplasma gondii DNA in CSF could contribute to the differential diagnosis of AIDS-related focal brain lesions, CSF samples from 88 HIV-infected patients (56 with focal brain lesions and 32 without) were tested prospectively by a nested PCR for the B1 gene of T. gondii. The assay had a detection limit of 10 trophozoite equivalents. Six of 18 patients with toxoplasmic encephalitis, but none of the 70 patients with other disorders, were PCR-positive (33.3% sensitivity and 100% specificity). Considering only those patients with cerebral toxoplasmosis from whom CSF was collected before or during the first week of antitoxoplasmic therapy, sensitivity rose to 50%. This was higher than the sensitivity in patients whose CSF was collected after the first week of treatment (odds ratio (OR) of 7.0; 95% CI: 0.46-218.2). The administration of antitoxoplasmic prophylaxis did not affect the PCR results. Patients with a poor response to therapy had a higher probability of detectable T. gondii DNA in their CSF (OR of 5.0; 95% CI: 0.37-86.6). All patients with other central nervous system disorders were PCR-negative. Despite the moderate sensitivity, the high specificity and positive predictive value (100%) make this assay a useful tool in the differential diagnosis of AIDS-related focal brain lesions as part of a series of CSF and neuroradiological examinations.
Several methods to increase the sensitivity of JC virus (JCV) DNA detection in cerebrospinal fluid (CSF) for a noninvasive diagnosis of AIDS-related progressive multifocal leukoencephalopathy (PML) were investigated. When CSF collected at clinical presentation was tested, JCV DNA was detected in 8 of 19 patients with PML by standard PCR (sensitivity, 42%; 95% confidence interval [CI], 21 to 66%) and in 14 of 19 by nested PCR (sensitivity, 74% [95% CI, 49 to 90%]; P = 0.014 [McNemar's test]. For multiple serial CSF samples, standard PCR yielded JCV DNA for 11 of 19 PML patients (sensitivity, 58% [95% CI, 34 to 79%]) and nested PCR yielded JCV DNA for 17 of 19 patients (sensitivity, 90% [95% CI, 66 to 98%]; P = 0.014). The majority of the false-negative samples were found to contain PCR inhibitors. Standard PCR did not detect JCV DNA in CSF from any of the 83 AIDS patients with other diagnosis (100% specificity [95% CI, 95 to 100%]); JCV DNA was found in CSF from one control patient by nested PCR (99% specificity [95% CI, 93 to 100%]).
Seventy-eight asymptomatic HIV-seropositive (aHIV) subjects were examined by means of an extensive neuropsychological test battery in comparison with 32 HIV-seronegative controls. They were also tested with regard to CD4+ and serum p24 antigen. Fifty-six of them completed a clinical follow-up of 12 up to 36 months and 35 also underwent a second session of neuropsychological, CD4+ and p24 antigen assessments at a 12- to 18-month interval from the first session. Results obtained lead to the following conclusions: (a) even among aHIV subjects there is a significant prevalence (28.2%) of cognitive abnormalities for which no cause other than HIV can be found, and therefore this suggests the possible development of HIV-related brain damage since the earliest stages of infection; (b) most sensitive to early HIV-related cognitive impairment are timed psychomotor tasks and memory tasks which require attention, learning and 'active' monitoring or retrieval of information; (c) during the early asymptomatic stages of HIV infection, there is no clear-cut evidence of a cross-sectional relationship between cognition and immunological/ virological markers (at least in the high ranges of CD4+ cell counts considered here); only in relatively more advanced stages does this relationship become evident in the subgroup of aHIV subjects with cognitive abnormalities; (d) the presence of cognitive abnormalities in early HIV infection is predictive of a further decrease in cognitive functioning and faster progression to AIDS-this latter reflected by a faster rate of decline in the number of CD4+ cells and by an increase in positivity of serum p24 antigen.
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Until now the different epidemiological studies performed have yielded widely different results in terms of the prevalence of hypertension in obese patients. This is mainly due to methodological errors in blood pressure (BP) measurements, including such false positives as white-coat or cuff hypertension, and more recently, to the different distribution in the study population of obese subjects at risk of hypertension (android obesity type). In 803 obese outpatient women (body mass index range: 28-45) randomly selected and subdivided into younger and older groups, and into android and gynaecoid, the casual BP was measured in the morning with a large size cuff. In addition, in 82 obese outpatients casual BP was measured simultaneously with the large and a standard size cuff. Another group of 94 patients was submitted to 24-h ambulatory blood pressure monitoring (ABPM). The aim was to observed if the use of inappropriate cuffs, or the incidence of white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The hypertension prevalence rate was 37.6% for the entire study group. The prevalence rate was 26.2% in women with gynaecoid type of obesity and 47.1% in android obese subjects. We could conclude that the use of inappropriate cuffs, office or white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The number of hypertensive subjects in younger obese subjects with gynaecoid fat distribution is similar to non-obese subjects who are age-adjusted, but our data confirm that the prevalence of hypertension in android type of obesity is significantly higher than in non-obese subjects.
BACKGROUND AND STUDY AIMS: The presumptive diagnosis of Candida esophagitis has been included in the Centers for Disease Control (CDC) case definition for full-blown AIDS since 1987. Endoscopic examination should be reserved for patients showing symptoms despite treatment. The purpose of this study was to assess the degree of diagnostic accuracy of the CDC presumptive clinical criteria and to determine the usefulness of upper digestive endoscopy in the diagnosis of Candida esophagitis in patients infected with HIV-1, with and without a previous AIDS-defining event. PATIENTS AND METHODS: A total of 144 HIV-1 infected patients who had undergone an upper digestive endoscopy were studied retrospectively. To determine the risk and the predictive value of the clinical markers, only the 84 patients without prior antimycotic therapy were included. RESULTS: Of the 84 patients without previous treatment, 34 (41%) had a history of an AIDS-defining illness. Candida esophagitis was found on endoscopy in 11 of the AIDS and 28 of the non-AIDS cases. Oral thrush, either alone (relative risk [R.R.] 9.4; 95% C.I. 2.4-36.4; p < 0.01; positive predictive value [PPV] 82%) or in combination with esophageal symptoms (R.R. 7.4; 95% C.I. 2.5-21.9; p < 0.01; PPV 89%), was a reliable marker of Candida esophagitis only in patients with a previous AIDS-defining event. The diagnostic value of the CDC presumptive pattern was confirmed by a multivariate analysis after controlling for the CD4 cell count (R.R. 9.3; 95% C.I. 2.3-25.3; p < 0.01). On the other hand, in HIV-1 positive patients without a previous AIDS-defining event, the diagnostic accuracy of oral candidiasis, either alone (R.R. 1.4; 95% C.I. 0.8-2.4; p n.s.; PPV 64%) or in combination with esophageal symptoms (R.R. 1.1; 95% C.I. 0.7-1.8; p n.s.; PPV 60%), was too low to allow a reliable diagnosis of Candida esophagitis. CONCLUSIONS: A presumptive diagnosis of Candida esophagitis on the basis of the CDC clinical criteria is a valid diagnostic method only in HIV-1 infected patients with a previous diagnosis of full-blown AIDS. Upper digestive endoscopy should be performed in symptomatic patients with no history of an AIDS-defining illness, especially if the diagnosis of esophageal candidiasis is important for surveillance purposes.
OBJECTIVE: To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection. DESIGN: Randomized, open label, prospective trial. SETTING: A single Infectious Diseases Department in Italy. PATIENTS: HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE. INTERVENTIONS: Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine). MAIN OUTCOME MEASURES: PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival. RESULTS: Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups. CONCLUSIONS: Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.
In order to verify whether fluconazole has a prophylactive effect against the occurrence of cryptococcosis in HIV-infected patients and to identify other factors capable of increasing or reducing the risk of this infection, we arranged a case-control study of 17 patients with cryptococcal infection. 34 controls were selected, matched by presence of an AIDS-defining event, CD4 cell count, and date of T-cell phenotyping. No significant difference in exposure to fluconazole, in total days of treatment, or in total dose administered was observed between cases and controls. However, control patients took a significantly higher average daily dosage of fluconazole and a linear tendency in risk reduction (p = 0.04) in relation to increasing dosage was observed. Antiretroviral therapy and an average daily fluconazole dose exceeding 150 mg both each reduced the risk of a cryptococcal infection.
In 46 female outpatients with android-type obesity, body mass index (BMI) 36.6 +/- 1.0, waist to hip ratio (WHR) > 0.86, and normal glucose tolerance (NGT) who were hypertensive at entry study [blood pressure (BP) > 140/90 mm Hg] and in 10 clinically healthy, nonobese, normotensive women, we evaluated the relationship between BMI, fat mass, WHR, fasting blood glucose, sum of blood glucose levels during oral glucose tolerance test and casual BP levels, 24-h ambulatory BP monitoring (ABP) parameters as the 24-hour mean, day-time mean, night-time mean and, by using a periodic model of cosine regression, MESOR (midline estimating statistic of rhythm), amplitude, acrophase, and baric impact. In android obese women, a negative correlation between ABP levels (day-/night-time, MESOR, and baric impact of systolic BP; night-time and MESOR of diastolic BP) and BMI has been documented. A positive correlation between systolic BP (casual, night-time mean, MESOR, amplitude, and baric impact), diastolic baric impact, and the WHR has been found. No correlation has been demonstrated between ABP monitoring parameters, and BMI, body fat, and WHR in the control group. Our data could suggest that, when enrolling obese subjects, it must be taken into account that obesity is a heterogeneous disorder. There are in fact obese subjects with normal or impaired glucose tolerance, as well as diabetics with moderate to severe obesity and with gynecoid or android-type obesity. In our android obese subjects with NGT, the WHR rather than the BMI was found to be a better predictor of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Involvement of the central nervous system (CNS) in patients with acquired immune deficiency syndrome (AIDS) is an increasing clinical problem. The most common brain complications are toxoplasmosis (50-70 per cent), primary CNS lymphoma (20-30 per cent) and progressive multifocal leucoencephalopathy (10-20 per cent). Almost two-thirds of these conditions can be treated, early diagnosis and therapy leading to survival with a good quality of life. Although clinical and neuroradiological criteria alone may have high predictive value, they are not sufficient to distinguish the broad spectrum of diseases reliably. Consequently, biopsy appears necessary for definite diagnosis in some cases. The potential role and timing of brain biopsy have been assessed. Twenty-four of 50 human immunodeficiency virus-seropositive patients with focal cerebral lesions were considered for biopsy between October 1991 and December 1992. Twelve underwent brain biopsy, seven stereotactic and five ultrasonographically guided. A diagnosis was achieved in 11 patients: six primary lymphoma, three progressive multifocal leucoencephalopathy, and one mycotic and one tuberculous abscess. Both techniques proved to be safe and reliable, with a 92 per cent diagnostic rate. These data confirm the usefulness of biopsy in patients with AIDS with its wide range of associated cerebral lesions that require different aggressive treatments. On the basis of this preliminary experience and reports in the literature, it is considered that brain biopsy is indicated for patients with focal enhancing cerebral mass lesions seen on computed tomography and magnetic resonance imaging who do not respond to an appropriate trial of empirical antitoxoplasmosis therapy and for those showing rapid clinical deterioration in whom imaging and serology do not suggest toxoplasmosis.
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The relationship of body mass index, body fat, waist to hip ratio, fasting blood glucose and sum of blood glucose levels during oral glucose tolerance test with casual blood pressure (BP) and BP parameters obtained by 24h ambulatory BP monitoring in 97 out-patients moderately obese (66 with android type obesity), normal glucose tolerance and mild hypertension at entry study, has been evaluated. A negative correlation between body mass index and systolic ambulatory BP levels as the 24h mean, daytime and nighttime, has been documented in all of the obese subjects; no correlations between body mass index and casual BP were shown. Only in the group of android type obese was the body mass index correlated positively with the casual DBP. Systolic 24h and nighttime BP values correlated positively with waist to hip ratio; the correlation coefficients improved in the subgroup of android type obese. By using 24h ambulatory BP monitoring, it may be possible to show that waist to hip ratio is a better predictor of systolic hypertension than other parameters such as those derived from weight and height measurements and body fat percentage.
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Fifty-five episodes of Pneumocystis carinii pneumonia (PCP) in AIDS patients were evaluated to assess clinical and laboratory risk factors predicting the probability of surviving the acute episode of PCP and the long-term survival after PCP. Age > 45 yrs, PaO2 < 50 mmHg, AaPO2 > 50 mmHg, and LDH > 800 IU/L correlated strongly with early mortality; patients who needed mechanical ventilation had a significantly lower PaO2 and serum albumin, and higher AaPO2 and LDH compared to the patients who did not. Neither age nor PaO2, AaPO2, LDH, albumin, days from onset, time for recovery, CD4+ cell count correlated with long-term survival of AIDS patients with PCP. Informations obtained at initial presentation of PCP may predict early outcome and influence therapeutic approach, improving chances for survival.
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