Discontinuing prophylaxis against Pneumocystis carinii pneumonia.
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Biomedical subjects
Publications and source records attributed to J P Breux.
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A 75-y-old woman with breast cancer presented with bacteremia due to Comamonas testosteroni. Evolution was favorable following adapted antimicrobial therapy and removal of a central venous catheter. This germ seems to be a rare pathogen; as reported in the literature, it is mostly encountered in patients with predisposing factors.
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The aim of this study was to evaluate the influence of age on the prognosis of infectious endocarditis. A retrospective study from 1987 to 1997 of 136 patients with infectious endocarditis on native, prosthetic valves or cardiac pacing catheter was performed. The outcome was analysed with the help of general practitioners. Two groups of patients were compared: 87 patients of 65 years of age or more (Group 1) and 49 patients under 65 years of age (Group 2). With a follow-up period of 5 years, the global mortality was 35%, but greater in Group 1 (p = 0.06). Cardiac failure was the main cause of death. The mortality was significantly higher in patients who were not operated (p < 0.002). The authors conclude that age of over 65 does not significantly worsen the prognosis of infectious endocarditis. The absence of surgery seems to be an indirect factor of a poor prognosis. Long-term follow-up of patients is necessary to diagnose and treat cardiac failure at an early stage and to consider referral for surgery.
The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.
In an ongoing, open-label, non-comparative study, the safety and efficacy of nevirapine/stavudine/didanosine were evaluated in 100 antiretroviral-naive adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV-1 RNA (pVL) > or = 5000 copies/ml. Sixty patients received nevirapine twice daily (VIRGO I) and 40 received nevirapine once daily (VIRGO II); all patients received didanosine once a day. After median follow-ups of 44 weeks in VIRGO I and 30 weeks in VIRGO II, the following virological results were observed (ongoing study): an intent-to-treat, non-completer equals failure analysis at week 24 showed the proportions of patients with pVL <500 copies/ml were 78% in VIRGO I (60% <50 copies/ml) and 75% in VIRGO II. An on-treatment analysis at week 52 showed 80% of patients with a pVL <500 copies/ml and 59% with <50 copies/ml in VIRGO I. The mean CD4 cell count increase was +171 cells/mm3 at week 24 and +218 cells/mm3 at week 52 in VIRGO I and +158 cells/mm3 at week 24 in VIRGO II. Cutaneous rash (grades 1 to 3) occurred in 24% of patients leading to nevirapine discontinuation in eight of 24 patients. Five other patients discontinued therapy during the first 24 weeks because of hepatic cytolysis, peripheral neuropathy or biological pancreatitis. The nevirapine/stavudine/didanosine combination is a convenient and safe regimen, with rapid and potent immunological and antiviral effects sustained over 12 months.
OBJECTIVE: To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART). DESIGN AND METHODS: A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event. RESULTS: Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis. CONCLUSION: In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.
The objective of this open-label trial is to evaluate the virological and immunological effects of triple therapy with stavudine (40 mg twice daily if > or = 60 kg, 30 mg twice daily if < 60 kg)/didanosine (400 mg once daily if > or = 60 kg, 300 mg once daily if < 60 kg)/nevirapine (200 mg daily from day 1 to 14, then 200 mg twice daily) in 60 antiretroviral-naive HIV-infected adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV RNA > or = 5000 copies/ml. At present, 59 patients have begun receiving the trial regimen. Characteristics of patients at baseline were as follows: 46 men/13 women, CDC stage A, 75%; mean CD4 cell count, 429 cells/mm3; mean HIV RNA, 4.6 log10 copies/ml). Mean decrease of viral load was -1.9 log10 at week 4 (n = 39), -1.9 log10 at week 16 (n = 20), with HIV RNA below the detectable level (< 500 copies/ml) in 62% of patients at week 4 and 85% at week 16. Mean CD4 cell count increase was +118 cells/mm3 at week 4. Cutaneous intolerance occurred within the first 4 weeks in 11/59 (19%) patients after a mean of 14 days (range, 3-24 days) and led to nevirapine discontinuation in 3/11 patients. Preliminary results of this ongoing trial show that combination therapy with stavudine/didanosine/nevirapine is a convenient (seven pills in two daily intakes) triple-therapy regimen with rapid immunological and antiviral effects. Rash, frequent in the first weeks of therapy, usually can be managed without stopping nevirapine. Long-term suppression of plasma HIV RNA with this combination needs to be confirmed but may support use of nevirapine as a component of first-line anti-HIV therapy along with two nucleosides.
Ten patients with neurological complications (NC) among a retrospective series of 53 consecutive cases of infective endocarditis were studied: 6 males and 4 females, mean age 60 years. NC were present at admission in 6 cases: 2 generalized seizures, 4 strokes, associated with 2 meningeal syndromes. Four cases of NC occurred during hospitalization: 1 stroke with come, 1 transient ischaemic attack, 2 generalized seizures. Blood cultures were positive in 7 cases: 6 group D Streptococci, 1 Gram negative bacillus. Five digestive portal of entry were identified. Cerebrospinal fluid was purulent in 1 patient, aseptic in 1, haemorragic in 2, and normal in 1. Cranial computed tomography revealed: infarct in 4 cases, brain abscess in 1 case, absence of abnormality in 1 case. There was no angiographic documentation. Antimicrobial therapy was maintained 5 to 6 weeks. Two patients underwent cardiac surgery. Two patients died of subarachnoid haemorrage. Comparison of patients with NC, and the 43 without NC, revealed two different point: vegetations were more frequent in the NC (8 cases out of 10) than without NC (19 cases out of 43) (p = 0.04). Streptoccus was often more found in NC (6 cases out of 6) than without NC (6 cases out of 24) (p < 0.01). Compared with the previously reported studies, where Staphylococcus was usually described, our results showed a higher frequency of Streptococcus D bovis, an older age, a higher frequency of stroke and digestive portal of entry. Vegetations were more frequent with NC than without.
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Botulism, a food-borne toxin-mediated disease caused by Clostridium botulinum is still a common disease, which is most frequent in the rural environment; 108 cases, 66 males and 42 females, average age 32 years, were recorded from 1965 to 1990 in the infectious disease department of the University Hospital of Poitiers (France). In 83% of patients, the food responsible was home-cured ham. Mean incubation time was 3.4 days; digestive symptoms were observed in 93% of cases, ocular symptoms in 92% and urinary tract dysfunction in 22%. A scale of severity was used to classify the patients into those suffering from severe (6), intermediate (50) and mild (52) forms of the disease. Botulinum toxin type B was found in 36 (52%) of 69 blood samples and in 41 (51%) of 81 samples of the suspected food. From 1965 to 1976, 44 patients were treated with both toxoid and heterologous equine serotherapy. Since 1976, 29 patients have been treated with guanidine hydrochloride (35 mg/kg daily) and 35 patients with guanidine hydrochloride plus heterologous serotherapy. All 108 patients recovered without any sequelae.
Fifty-three cases of infective endocarditis are reported: 10 definite, 33 probable, 10 possible. There were: 35 males, 18 females, mean age: 66 +/- 14 years. Twenty-three patients had a known valve involvement, 21 a recently diagnosed valve involvement, 9 a prosthetic valve. Fifty patients had fever, 43 had a regurgitating murmur, 28 weakness and weight-loss, 13 cutaneous lesions, 11 arthritis, 8 splenomegaly, 3 ocular lesions. The portal of entry was suspected or confirmed in 37 cases: intestinal in 12 cases, dental in 11 cases, cutaneous in 7 cases, urinary tract infection in 6 cases, upper respiratory tract infection in 1 case. The micro-organism was found in 45 cases: 10 oral streptococci, 12 D bovis streptococci, 6 enterococci, 5 aureus staphylococci, 3 coagulase-negative staphylococci, 2 Coxiella burnetii, 7 other bacterias. Blood-cultures were negative in 8 cases. Precordial echocardiography found vegetations in 27 native valves and 9 prosthetic alterations. Ten patients had neurologic complications, 27 cardiac complications, 8 acute renal failure. Nine patients needed cardiac surgery, 6 died. Our results, compared with those in the literature, showed older age, a higher frequency of digestive portal of entry and of D bovis streptococci, frequently associated with a colic tumour.
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Endogenous event-related potentials (and especially the P300 component) have delayed latencies relative to normal controls in patients with dementias of diverse aetiologies. Moreover, the subcortical varieties of dementia tend to affect also the early-stage N1 and P2 components whereas both types of dementias affect the later-stage N2 and P3 components. However it has become obvious that patients with HIV infection are susceptible to develop progressive, AIDS-related dementia, renamed 'HIV encephalopathy' by the Center for Disease Control. Several studies have shown that endogenous, but also early, components of long latency auditory evoked potentials are prolonged in latency in HIV-demented patients. However, these changes may also be present in class II and III patients and may permit the early recognition of HIV encephalopathy.
One of the new criteria of positivity of exercise stress testing proposed by Detrano and Kligfield is the ST/HR index, obtained by calculating the ratio of additional ST depression on exercise over the corresponding variation in the heart rate. These authors reported that this ratio improved the diagnostic value of the exercise stress test with respect to the traditional ST segment depression, but that the proportion depended on whether the index was measured 80 or 60 ms after the J point. The object of this study was to assess the diagnostic performance of the ST/HR index measured 0, 20, 40, 60 and 80 ms after the J point by automatic analysis and to compare these five diagnostic indices with the classical ST segment depression (standard criterion) by ROC graphs and the Mac Nemar test. One hundred consecutive patients (73 men and 27 women) all symptomatic, underwent submaximal or symptom-limited exercise stress testing and accepted coronary angiography. The prevalence of greater than or equal to 50% coronary stenosis on at least one main vessel was 48%. None had previous myocardial infarction. The ROC graphs and areas under the curve demonstrated generally the superiority of the ST/HR index over the standard criteria. The optimal diagnostic performance was observed when the index was calculated 20 ms after the J point (ST 20/HR index).(ABSTRACT TRUNCATED AT 250 WORDS)
Neuropsychological and psychometric investigations have sometimes attested to and sometimes denied the existence of cognitive perturbations during the early phases of human immunodeficiency virus (HIV) infection (stages II and III of the CDC classification): strictly asymptomatic seropositivity or generalized lymphadenopathy. Therein lies the basis of the debate concerning the neurotropism of the virus and its deleterious effects on the central nervous system (CNS). We hoped to contribute to the resolution of this discussion by recording late evoked auditory potentials, which are composed of two types of components: exogenous responses attesting to the reception of stimuli by specific sensory areas of the CNS, regardless of their informative value for the subject; and endogenous responses that occur later, appearing when the subject is required to distinguish between different stimuli, for example, counting high-pitched sounds randomly distributed among low-pitched ones. The latter responses, which have been most extensively studied for wave P300, are associated with cognitive functions, and alterations of the evoked cognitive potentials have been observed during the course of demential syndromes of various origins. Fifteen individuals were subjected to the protocol for recording long-latency, evoked auditory potentials. These studies were completed by a battery of psychometric tests, two methods for evaluating depression and an assessment of the anxiety level. The results showed a significant lengthening of the latency of wave P300 in the seropositive subjects. This prolongation also affected one of the exogenous components, i.e., wave P2. In addition, their intelligence quotients, regardless of whether the IQ explores the so-called crystallized component or the fluid component of intelligence, were not significantly different from those of the general population.(ABSTRACT TRUNCATED AT 250 WORDS)