Biomedical subjects
J de Gans
Publications and source records attributed to J de Gans.
Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos.
We carried out a meta-analysis of 22 trials to determine the comparative placebo effect of (a) subcutaneous vs. oral and (b) in-hospital vs. at-home administration in the treatment of migraine. The headache relief rates were combined from the placebo arms of these randomised clinical trials assessing the value of sumatriptan in acute treatment of migraine. The main outcome measure was the proportion of patients reclassified from severe or moderate headache severity to no or mild headache severity 2 h after the beginning of treatment. In the oral regimen 222 of 865 patients (25.7%) reported no or mild headache severity after 2 h, compared to 279 of 862 patients (32.4%) of those receiving subcutaneous placebo (6.7% difference; 95% CI 2.4-11.0%). Adjusting for treatment setting and severity of headache at baseline did not change the observed difference. After placebo treatment at home 285 of 1,054 patients (27.0%) reported no or mild headache severity after 2 h, compared to 216 of 673 patients (32.1%) among those receiving placebo in hospital (5.1 % difference; 95% CI 0.6-9.5%). When adjusted for route of administration and severity of headache at baseline, the difference in relief rates between home and hospital setting disappeared. These findings indicate that subcutaneous administration enhances the placebo effect of acute treatment of migraine. Future trials of antimigraine drugs assessing the relative efficacy of various routes of administration should use a double-dummy technique. The interpreting of placebo-controlled trial results must therefore consider that the effect in the drug arm of the trial depends in part on the route of administration.
Meningitis due to viridans streptococci in adults.
Seven patients are reported with meningitis due to viridans streptococci. These patients represented 5% of culture-proven cases of bacterial meningitis in adults participating in a prospective multicentre clinical trial evaluating the use of dexamethasone. Meningitis was iatrogenic in three patients: one patient had been treated with endoscopic sclerotherapy for oesophageal varices, and two patients had undergone thermocoagulation of the gasserian ganglion for trigeminal neuralgia in the previous days.
Meropenem susceptibility of Neisseria meningitidis and Streptococcus pneumoniae from meningitis patients in The Netherlands.
In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest. Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined. Rifampicin susceptibility was additionally tested for N. meningitidis. Of the meningococci, 4.3% were of intermediate resistance to penicillin and 0.3% were resistant to rifampicin. One pneumococcal isolate (0.6%) was of intermediate resistance to penicillin. All strains were susceptible to meropenem. We conclude that meropenem is in vitro highly active against N. meningitidis and S. pneumoniae.
Management of acute bacterial meningitis.
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Brain infarcts in adults with bacterial meningitis.
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[Listeria meningitis in adults].
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Antimicrobial susceptibility of Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae isolates causing meningitis in The Netherlands, 1993-1994.
The increasing antimicrobial resistance among pathogens frequently isolated from patients with bacterial meningitis formed the rationale to perform a surveillance study to determine the prevalence of resistance in The Netherlands. Haemophilus influenzae strains (n = 316) isolated from cerebrospinal fluid (CSF), 1125 meningococcal strains isolated from blood or CSF and 398 pneumococcal strains isolated from CSF in 1993 and 1994 were tested by the Etest for susceptibility to commonly prescribed antibiotics for the treatment of community-acquired meningitis. In H. influenzae strains ampicillin-resistance occurred in 7.0%, resistance to chloramphenicol in 2.2%, and resistance to both antibiotics in 0.9%. The prevalence of intermediate penicillin-resistance in meningococci was 3.3%. Resistance to rifampicin was rarely found (0.1%). Intermediate penicillin-resistance in pneumococci was found in only 0.5% of isolates. All 1839 isolates were susceptible to ceftriaxone. Based on these results, we conclude that empirical therapy of childhood community-acquired bacterial meningitis with amoxycillin and chloramphenicol is no longer justified in children who have not been vaccinated against H. influenzae type b. In vaccinated or older children and adults, amoxycillin is a rational choice for empirical treatment of meningitis. The prophylactic use of rifampicin in contacts of patients with meningococcal disease is still applicable.
[Supplemental treatment of bacterial meningitis with corticosteroids still insufficiently founded].
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[The many aspects pf the acid-fast rods].
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Presentation and course of AIDS dementia complex: 10 years of follow-up in Amsterdam, The Netherlands.
OBJECTIVE: To assess the clinical presentation and course of the AIDS dementia complex (ADC). DESIGN: Retrospective study of a consecutive series of symptomatic HIV-1-infected patients [Centers for Disease Control and Prevention (CDC) stages IVA, B, C and D] evaluated for neurological symptoms between 1982 and 1992. SETTING: An academic referral centre for AIDS. PATIENTS: A total of 536 symptomatic HIV-1-infected patients evaluated for neurological symptoms between 1982 and 1992. INTERVENTIONS: Zidovudine treatment, which was introduced in The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (CDC stages IVA, B, C and D). MAIN OUTCOME MEASURES: Diagnosis of ADC and CD4 cell count, clinical features, neuropsychological abnormalities, computed tomography (CT) and magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid (CSF) findings and course in patients with ADC. RESULTS: ADC was diagnosed in 40 out of 536 (7.5%) immunosuppressed, neurologically symptomatic HIV-1-infected patients in CDC stage IV, and was the AIDS-defining illness in six. The mean CD4 cell count of the 40 patients with ADC was 109 x 10(6)/l. Neuropsychological abnormalities in 15 out of 17 patients tested were in accordance with subcortical dementia. On CT scan of the brain, 70% showed no or only mild cortical atrophy. MRI was more sensitive than CT scan for detecting white matter abnormalities (73 versus 35%; P = 0.02). CSF examination showed mononuclear pleocytosis in 25%, protein level increase in 55%, and HIV-1 p24 core protein in 38% (13 out of 34). The mean survival was 6.7 months in the 40 ADC patients, but 4 months in 20 patients who had never used zidovudine, compared with 14.8 months in 10 patients who started zidovudine after they were classified as having ADC (P < 0.001). Three of these 10 patients improved remarkably, and two slightly, after starting zidovudine. ADC developed after discontinuation of zidovudine in nine patients. Only one patient developed ADC while receiving 600 mg zidovudine. CONCLUSIONS: MRI is more sensitive than CT for detecting white matter abnormalities. To date, there is no specific or sensitive CSF marker for ADC. Zidovudine may improve symptoms and prolong survival in patients with ADC, which rarely developed with continued zidovudine use in our study.
Ganciclovir/foscarnet for cytomegalovirus meningoencephalitis in AIDS.
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Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis.
OBJECTIVE: We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment. DESIGN: The trial was a prospective, randomized, and non-blinded study. SETTING: The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands. PATIENTS, PARTICIPANTS: Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis. INTERVENTIONS: Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients. MAIN OUTCOME MEASURES: Outcome measures were a complete or partial response, recrudescence and relapse. RESULTS: A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003). CONCLUSION: Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.
Disseminated actinomycosis due to Actinomyces meyeri and Actinobacillus actinomycetemcomitans.
A 44-year-old man presented with pulmonary lesions and neurological symptoms suggestive of lung carcinoma with cerebral metastases. He had non-specific chest X-ray findings since 6 years and he also suffered from relapsing purulent skin lesions which resolved spontaneously or by short courses of antibiotic treatment. When corticosteroids were given, multiple subcutaneous swellings developed that spontaneously ruptured. The pus contained Actinomyces meyeri and Actinobacillus actinomycetemcomitans. On operation, the intracerebral lesions appeared to be abscesses and the same bacteria were cultured as from the skin lesions. Bronchoscopical examination did not reveal a diagnosis. Amoxicillin was given for 12 months and the patient recovered.
Pyrimethamine alone as maintenance therapy for central nervous system toxoplasmosis in 38 patients with AIDS.
We retrospectively assessed the efficacy of maintenance therapy with pyrimethamine alone in 38 patients with AIDS and central nervous system (CNS) toxoplasmosis. The diagnosis was based on clinical presentation and compatible CT scan abnormalities with subsequent response to therapy. Survival analysis was performed by the product limit method of Kaplan-Meier. Fourteen patients received maintenance therapy with 25 mg pyrimethamine per day (group 1), and 24 patients were treated with 50 mg per day (group 2). The median survival from initiation of maintenance therapy until death or end of the study for the entire study population was 32 weeks. Median survival in group 1 was 28 weeks, as compared with 36 weeks in group 2 (p = 0.34). Relapses occurred in 12 patients, six in group 1 and six in group 2. There was no significant difference in failure-free survival between the two treatment groups (p = 0.09). One patient in group 1 and two patients in group 2 experienced severe toxicity, requiring discontinuation of therapy. All three patients relapsed and died. Two patients in group 2 who stopped treatment on their own initiative also had relapses. Thus, all five patients who discontinued therapy had relapses. Five of 13 patients in group 1 and two of 20 patients in group 2 relapsed during continuous therapy with pyrimethamine (p = 0.13); these seven patients responded to reintroduction of combination therapy (n = 6) or treatment with 50 mg pyrimethamine per day (n = 1). The results of our retrospective analysis suggest that maintenance therapy with oral pyrimethamine, 50 mg per day, in AIDS patients with CNS toxoplasmosis is effective.
Mental changes in patients with AIDS.
Mental changes are common in patients with acquired immunodeficiency syndrome (AIDS). Neuropsychological data of 32 patients with AIDS and cognitive symptoms were reviewed. All patients were neurologically examined and ancillary investigations were performed. According to the neuropsychological data three groups could be distinguished: I) 4 patients with dementia and cortical deficits; II) 16 patients with subcortical dementia; III) 12 patients with subcortical cognitive deficits without global intellectual deterioration. AIDS Dementia Complex (ADC) was diagnosed in 12 patients and occurred in all three groups. The most frequent form of dementia in patients with AIDS is of a subcortical type. Impaired memory or reduced psychomotor speed, or both, are common in patients without global intellectual deterioration. ADC seems an unlikely diagnosis in patients with cortical dementia. Neuropsychological examination is important for diagnosing ADC but the diagnosis cannot be made without regarding the neurological findings and ancillary investigations.
Therapy for cytomegalovirus polyradiculomyelitis in patients with AIDS: treatment with ganciclovir.
Six AIDS patients with progressive cytomegalovirus (CMV) polyradiculomyelitis were treated with ganciclovir in an open study. The diagnosis was based on the presence of a distinct clinical syndrome with progressive flaccid paraparesis, preserved proprioception and urinary retention with specific cerebrospinal fluid (CSF) findings. Ganciclovir therapy, 5-10 mg/kg per day, instituted 3-6.5 weeks after onset of symptoms, was ineffective in four patients with severe paraparesis. One patient developed CMV polyradiculomyelitis while receiving ganciclovir and further deteriorated during foscarnet therapy. One patient however, showing minor paresis of one leg, improved after institution of ganciclovir therapy 1 week after onset of symptoms. It is concluded that a presumptive diagnosis of CMV polyradiculomyelitis can be made on the basis of distinct clinical findings and CSF pleocytosis with predominance of polymorphonuclear leukocytes in patients with AIDS. Ganciclovir therapy does not appear to be beneficial for patients with advanced paresis in the doses used. Further investigations are needed in order to determine if early intervention with ganciclovir, when paresis is mild, or higher doses in advanced paresis, might be of some benefit.
Predominance of polymorphonuclear leukocytes in cerebrospinal fluid of AIDS patients with cytomegalovirus polyradiculomyelitis.
Cytomegalovirus (CMV) polyradiculomyelitis was diagnosed in 4 of 241 consecutive neurologically assessed human immunodeficiency virus type (HIV-1) seropositive patients. CMV-related neurologic disease was suspected on clinical grounds and was subsequently confirmed by CMV culture from cerebrospinal fluid (CSF) and/or CMV in situ hybridization on specific specimens. All four patients showed CSF pleocytosis with predominance of polymorphonuclear leukocytes (PMNs). Retrospective analysis of the results of CSF examination, performed in 143 of 241 patients with neurologic symptoms, showed pleocytosis in 58 of 143 patients. Predominance of PMNs was found in seven patients, including the four with CMV polyradiculomyelitis. It is concluded that in HIV-1 seropositive patients with a clinical diagnosis of polyradiculomyelitis, a predominance of PMNs in CSF could be an indication that the condition is CMV related. This should lead to early diagnosis and institution of specific antiviral therapy.