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Biomedical subjects

P J de Vries

Publications and source records attributed to P J de Vries.

At least 19 recordsLinked to original sources

[Miltefosine: a new remedy for leishmaniasis].

There is a need for a safe and effective oral treatment for cutaneous and visceral leishmaniasis. Miltefosine is the first oral drug that is efficacious against different forms ofleishmaniasis, however it is not equally effective against all Leishmania species. Miltefosine is an alkylphosphocholine, originally developed for the treatment of cancer. The mechanism of action is probably based on interference with the synthesis and degradation of parasitic membrane lipids. Little is known about the pharmacokinetics ofmiltefosine; an important characteristic is its long elimination half-life of seven days or longer. The most frequent adverse effects are of gastrointestinal origin. Miltefosine should not be used during pregnancy. Over thirty leishmaniasis patients have already been treated with miltefosine in the Netherlands.

Animals↗

Quantification of the response to miltefosine treatment for visceral leishmaniasis by QT-NASBA.

A male patient with psoriatic arthritis and visceral Leishmania infantum infection was treated with oral miltefosine 50 mg three times a day for 4 weeks at the Academic Medical Center, Amsterdam, The Netherlands. Miltefosine plasma concentrations were measured with liquid chromatography/mass spectrometry. The parasite load was followed by quantitative nucleic acid sequence-based amplification (QT-NASBA) assay in blood. Miltefosine elicited a prompt therapeutic effect. After an initial worsening of symptoms and an increase of QT-NASBA values during the first week, recovery was rapidly achieved. QT-NASBA values declined exponentially and were negative after 6 weeks. Miltefosine plasma concentrations continued to accumulate during the 4 weeks of treatment. The terminal elimination half-life was 14.8 days.

Administration, Oral↗

Neuroanatomical correlates of memory deficits in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a multisystem syndrome classically associated with the occurrence of focal brain dysplasias. We used structural magnetic resonance imaging to test for neuroradiological abnormalities in TSC (tubers, white matter lesions, and subependymal nodules) and to explore the relationships between these lesions and computational morphometric abnormalities of gray and white matter distribution. We tested memory function in TSC and investigated the relationship between memory function and both morphometric variation and lesion load. Patients demonstrated deficits bilaterally in volume of subcortical gray matter regions including thalamus, basal ganglia, insula, and cerebellum, as well as white matter deficits bilaterally in intrahemispheric tracts. Morphometric deficits could not be explained as local effects of lesions. Patients demonstrated deficits in executive working memory and recall memory, sparing recognition. Structure-function mapping showed long-term and working memory function was positively correlated with gray matter density (in thalamus, caudate nucleus, and frontal cortex) but not with lesion load. The neuroanatomical endophenotype of TSC is more extensive than previously recognized and comprises abnormalities in the distribution of gray and white matter in addition to classical lesions. Normal intelligence quotient patients with TSC show a profile of long-term and working memory impairment that is related to gray matter deficits in thalamus and basal ganglia components of fronto-striatal circuits.

Adult↗

The cognitive and behavioural phenotype of Roifman syndrome.

BACKGROUND: Roifman syndrome (OMIM 300258) is a multi-system disorder with a physical phenotype that includes Beta-cell immunodeficiency, intra-uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy and characteristic facial dysmorphism. So far, six cases, all boys, have been reported in the literature. Roifman postulated that the syndrome may be due to a mutation in an X-linked gene or an autosomal gene giving rise to a sex-limited trait, but the definitive pathogenetic mechanism has still not been elucidated. Very little is known about the cognitive and behavioural phenotype of Roifman syndrome and no standardized measures of cognitive abilities have been reported. METHODS: We report the seventh case of a boy with Roifman syndrome and present the first systematic documentation of the cognitive and behavioural phenotype of an individual with the syndrome. RESULTS: In spite of having been reported as appearing intellectually 'able', formal evaluation showed very significant intellectual disability and neuropsychological impairment across cognitive domains. CONCLUSIONS: The findings suggest that Roifman syndrome may be an example of an X-linked mental retardation syndrome (XLMRS).

Child↗

Acute pulmonary histoplasmosis from Ghana.

A male patient developed acute pulmonary histoplasmosis 2 weeks after bathing in the water falls of Wli, Ghana. Exposure to Histoplasma capsulatum was probably mediated through inhalation of an aerosol of water and guano from the large colony of fruit bats of the falls. More cases of acute pulmonary histoplasmosis can be expected.

Acute Disease↗

Nutritional status following malaria control in a Vietnamese ethnic minority commune.

OBJECTIVE: To study whether control of malaria leads to catch-up growth or an increase of obesity in a marginally nourished population. SETTING: A Vietnamese ethnic minority commune in southern Vietnam. DESIGN: Repeated annual anthropometric surveys were performed from 1995 to 2000. Z-scores for height, weight and BMI for age and weight-for-height were determined by using NCHS 1978 and CDC 2000 reference tables and by the LMS method. INTERVENTION: Active malaria control that reduced the parasite carrier rate from 50% in 1994 to practically nil in 1998. RESULTS: Inhabitants were generally of short stature and very thin. Using the US reference tables, the prevalence of moderate/severe stunting among children was 53/24% and of wasting 27/9% in the first survey in 1995. Physical condition and normal daily activities of most inhabitants were normal. The repeated LMS-Z-scores uncovered a significant recovery of stunting, extending into preadolescence, including the development of a pubertal growth spurt for girls and enhancement of pubertal growth in boys, after control of malaria. The mean (95% CI) annual increase of Z-height-for-age was 0.11 (0.09-0.12) for boys and 0.14 (0.13-0.15) for girls (P<0.001). As a consequence, weight-for-age and BMI Z-scores decreased without indication of developing obesity. CONCLUSION: Catch-up growth, extending into preadolescent age, was observed in a Vietnamese ethnic minority population with a chronic state of low food intake, without indication of developing obesity. The control of malaria was probably the most significant contribution to this catch-up growth.

Adolescent↗

[Cutaneous nocardiosis as an opportunistic infection].

A 46-year-old man who had been treated with azathioprine and budesonide for Crohn's disease for the past eight years developed a purulent skin condition on the right ring finger. Despite surgical drainage and treatment with amoxicillin and flucloxacillin, the condition spread itself over the hand and lower arm, partly per continuum and partly in jumps. The patient did not feel ill and there were no systemic symptoms. Ultimately, Nocardia asteroides was cultured from the wound and complete cure was achieved after 8 months' treatment with co-trimoxazole. Infections with Nocardia spp. are rare but may occur more often and run a more fulminant course in patients under treatment with immunosuppressants. Cutaneous nocardiosis generally has a characteristic lymphogenous spreading pattern, but an atypical picture with pustules, pyoderma, cellulitis or abscess formation is also possible. In non-cutaneous nocardiosis there is usually pneumonia or lung abscess, possibly with secondary haematogenous spread to the central nervous system or skin. Culturing Nocardia requires more time than usual but can be promoted by special culture media. Treatment of the infection with co-trimoxazole is the method of choice and is almost always successful in cases of cutaneous nocardiosis.

Anti-Infective Agents↗

Rapid serological assays for leptospirosis are of limited value in southern Vietnam.

Leptospirosis, although ubiquitous and potentially lethal, is often not diagnosed. The seroprevalence of anti-Leptospira antibodies and the utility of two rapid tests for the serodiagnosis of the disease were studied in Binh Thuan, an area in southern Vietnam with favourable conditions for Leptospira. In an initial survey, blood samples from 44 patients with undifferentiated fever and 83 healthy subjects were each examined for anti- Leptospira antibodies using three tests: an ELISA; a latex card-agglutination test (Dri Dot); and a lateral-flow assay (LeptoTek Lateral Flow). In the ELISA, samples from 35% of the healthy subjects and 40% of the febrile patients were found to have titres of anti- Leptospira IgM of at least 1:80. Only one of the 13 patients checked again, in ELISA, 3 weeks later, showed the marked increase in IgM titre that is indicative of acute leptospirosis. In the initial survey, although the positive results of the lateral-flow assay, applied to whole blood and serum, showed a good agreement with those of the ELISA (kappa = 0.743), the results of the lateral-flow assay were often indeterminate. The card-agglutination test was more specific. The overall agreement between the results of the rapid tests and those of the ELISA was generally poor. When the samples classified as 'indeterminate' in the lateral-flow assay were considered positive, the maximum kappa-value for this assay applied to whole blood was only 0.512. In conclusion, it appears that high seroprevalences of anti- Leptospira IgM and low incidences of acute leptospirosis limit the diagnostic value of the rapid tests that were investigated. The lateral-flow assay is not specific enough. The card-agglutination test is possibly better but, because of the low incidence, its sensitivity could not be evaluated adequately in the present study.

Adolescent↗

Usefulness of quantitative nucleic Acid sequence-based amplification for diagnosis of malaria in an academic hospital setting.

The aim of the present study was to evaluate the usefulness of quantitative nucleic acid sequence-based amplification (QT-NASBA) to detect Plasmodium spp. in diagnostic specimens of patients suspected of having malaria in a clinical setting in a non-endemic country. During the 4-month recruitment period, 113 patients were enrolled in the study, of which 93 were diagnosed as non-malaria and 20 as malaria cases on the basis of clinical and microscopic criteria. All microscopically positive cases had QT-NASBA counts of >0.1 parasites/ micro l and there was a significant positive correlation between the parasite counts obtained with both diagnostic methods. Of the 93 microscopically negative cases, six had a positive QT-NASBA result. Three of these cases had a recent history of malaria for which specific treatment was taken. In the other three cases there was no history of malaria and QT-NASBA results in these cases were near the cut-off level (>0.1 parasites/ micro l) of the test. The results demonstrate that QT-NASBA is a useful technology for the diagnosis of malaria in a reference laboratory, and it is very helpful in cases of low parasitemia.

Academic Medical Centers↗

[Migrating subcutaneous swellings due to dirofilariasis after a visit to the South of France].

In two women, aged 59 and 31 years, who suffered from an itching cutaneous nodule, subcutaneous dirofilariasis was diagnosed. The disease is characterised by recurrent migrating subcutaneous nodules and swellings. Both patients recently visited the South of France. Laboratory examination revealed a moderate eosinophilia. In both patients, filaria antibodies were demonstrated during the course of the disease and a nodule was eventually resected. Parasitological examination revealed Dirofilaria repens. After this the swellings did not recur. Dirofilariasis is a zoonosis common in dogs and cats, and is transmitted by mosquitoes. In humans, the most common clinical manifestation is a migrating subcutaneous nodule in the case of D. repens, and a pulmonary infiltrate (coin lesion on radiographs) in the case of Dirofilaria immitis. Filarial serology is often positive. The diagnosis is confirmed by parasitological examination of the excised nodule. Dirofilariasis is usually innocuous; it disappears after the worm has died but can cause patients to worry.

Adult↗

[Migrating swellings from Asia: gnathostomiasis].

Two patients suffered from intermittent subcutaneous swellings of the face. A 41-year-old man recalled a recent episode with severe thoracic pain and at that time pleurisy was documented. In this patient there was pronounced eosinophilia. The other was a 32-year-old woman. Both patients had traveled to southeast Asia. Antibodies against Gnathostoma spinigerum were detectable in both patients. The first patient was treated with albendazole 200 b.i.d. for three weeks, but because of recurrent facial swelling, he was treated again with albendazole at a higher dose: 400 b.i.d. for eight weeks, which the swellings did not recur. The second patient was not treated because the frequency of the swellings had already decreased spontaneously. Gnathostomiasis is an infection by the nematode G. spinigerum. The main route of human infection is by eating insufficiently not well-cooked fish or frog. The initial infection is often not recognised, but severe symptoms can occur. In humans, the larva of the nematode does not develop further but may wander through the subcutaneous tissues. Untreated, the infection usually runs a mild, self limiting course, but complications such as invasion of the central nervous system or of the eye have been described. Treatment with albendazole reduces recurrence of swellings.

Adult↗

Delay of natural bone loss by higher intakes of specific minerals and vitamins.

For early prevention or inhibition of postmenopausal and age-related bone loss, nutritional interventions might be a first choice. For some vitamins and minerals an important role in bone metabolism is known or suggested. Calcium and vitamin D support bone mineral density and are basic components in most preventive strategies. Magnesium is involved in a number of activities supporting bone strength, preservation, and remodeling. Fluorine and strontium have bone-forming effects. However, high amounts of both elements may reduce bone strength. Boron is especially effective in case of vitamin D, magnesium, and potassium deficiency. Vitamin K is essential for the activation of osteocalcin. Vitamin C is an important stimulus for osteoblast-derived proteins. Increasing the recommended amounts (US RDA 1989), adequate intakes (US DRI 1997), or assumed normal intakes of mentioned food components may lead to a considerable reduction or even prevention of bone loss, especially in late postmenopausal women and the elderly.

Ascorbic Acid↗

Dementia as a complication of schizophrenia.

OBJECTIVES: Cognitive impairment is known to occur in schizophrenia, and may be marked in institutionalised patients. The aim of this study was to determine whether it ever warrants an additional diagnosis of dementia. METHODS: A population of chronic schizophrenic patients who were aged 65 or younger and showed no organic risk factors for dementia were screened for presence of disorientation. Any showing this underwent neuropsychological testing, physical investigations, and structural and functional neuroimaging. Information about day to day cognitive function was also obtained from carers. RESULTS: Eight patients aged 28 to 64 were identified who showed disorientation; in all cases this was accompanied by general intellectual impairment and objective evidence of a dementia syndrome. The patients' schizophrenic symptoms were unexceptional and did not seem sufficient to account for their cognitive impairment. Neuropsychological testing disclosed relative sparing of visual and visuospatial function and language syntax, but pervasive deficits in memory and executive function. Brain CT demonstrated only minor abnormalities but most of the patients showed frontal or temporal hypoperfusion on SPECT. CONCLUSIONS: Dementia in schizophrenia seems to be a real entity with a neuropsychological signature similar to that of frontotemporal dementia. Functional but not structural imaging abnormalities may also be characteristic.

Adult↗

Pharmacokinetic interactions of antimalarial agents.

Combination of antimalarial agents has been introduced as a response to widespread drug resistance. The higher number of mutations required to express complete resistance against combinations may retard the further development of resistance. Combination of drugs, especially with the artemisinin drugs, may also offer complete and rapid eradication of the parasite load in symptomatic patients and thus reduce the chance of survival of resistant strains. The advantages of combination therapy should be balanced against the increased chance of drug interactions. During the last decade, much of the pharmacokinetics and metabolic pathways of antimalarial drugs have been elucidated, including the role of the cytochrome P450 (CYP) enzyme complex. Change in protein binding is not a significant cause of interactions between antimalarial agents. CYP3A4 and CYP2C19 are frequently involved in the metabolism of antimalarial agents. Quinidine is a potent inhibitor of CYP2D6, but it appears that this enzyme does not mediate the metabolism of any other antimalarial agent. The new combinations proguanil-atovaquone and chlorproguanil-dapsone do not show significant interactions. CYP2B6 and CYP3A4 are involved in the metabolism of artemisinin and derivatives, but further studies may reveal involvement of more enzymes. Artemisinin may induce CYP2C19. Several artemisinin drugs suffer from auto-induction of the first-pass effect, resulting in a decline of bioavailability after repeated doses. The mechanism of this effect is not yet clear, but induction by other agents cannot be excluded. The combination of artemisinin drugs with mefloquine and the fixed combination artemether-lumefantrine have been studied widely, and no significant drug interactions have been found. The artemisinin drugs will be used at an increasing rate, particularly in combination with other agents. Although clinical studies have so far not shown any significant interactions, drug interactions should be given appropriate attention when other combinations are used.

Animals↗

Artemisinin for treatment of uncomplicated falciparum malaria: is there a place for monotherapy?

The efficacy of artemisinin monotherapy was studied in 227 patients with uncomplicated falciparum malaria. They all received artemisinin at t = 0 hr, t = 8 hr, and thereafter once daily; treatment was extended at random until they had taken either 5 days of artemisinin followed by 2 days of placebo (A5), or 7 days (A7) of artemisinin. The adult artemisinin dose was 500 mg; children aged < 15 years received 10 mg/kg per dose. The median (range) parasite clearance time was 39 (8-112) hr for A5 and 43 (38-104) hr for A7 (P = 0.085). The recrudescence rates were similar between the groups. The lowest parasite count achieved during treatment (Pterm) was associated with the occurrence of recrudescence (P = 0.046, Cox regression model); it was lower for patients with a radical cure or late recrudescence than for early recrudescence (P = 0.034, t-test). Artemisinin monotherapy may offer rapid recovery and fast parasite clearance, but recrudescence is frequent. Extending the duration of monotherapy from 5 days to 7 days does not reduce recrudescence.

Adolescent↗

[Tropical diseases and imported disorders in 1763 patients seen at the Outpatient Clinic for Tropical Diseases, Academic Medical Center, Amsterdam (1996-1997)].

OBJECTIVE: To describe an analysis of the patients seen at the Outpatient Department (OPD) for Tropical Diseases in the Academic Medical Centre, Amsterdam, during 1996 and 1997. DESIGN: Descriptive cross-sectional study. METHOD: From our database of OPD-patients the following data were analysed: age, country of birth, travel destination and most frequent complaints at presentation. These were further analysed in relation to travel destination, diagnosis and need of admission. RESULTS: In 1996 and 1997 1763 patients visited the OPD. Abdominal complaints, fever, general malaise and skin diseases were the main problems. Abdominal complaints were more often acquired in Asia, fever in sub-Saharan Africa and skin problems in South America. General malaise was not related to a specific travel destination. Abdominal complaints, fever and general malaise were more often caused by parasites, and skin problems by bacteria. Plasmodia were the most frequently encountered microbial cause. Malaria was found in 1 out of every 3 Dutch, and 9 out of every 10 Ghanaian patients with fever from Africa. CONCLUSION: The analysis of the database yielded useful information regarding patients with import diseases in the Netherlands and with respect to travellers to tropical areas.

Academic Medical Centers↗

[Why is malaria in Vietnam under control, but Africa is threatened with a malaria disaster?].

In Africa malaria parasites are increasingly developing resistance to the 3 affordable and tolerable drugs: chloroquine, amodiaquine and sulfadoxine-pyrimethamine. Alternative products are much more expensive and more toxic. A malaria disaster is looming. On the contrary, in Vietnam a disaster appears to have been averted. Data on malaria epidemiology, on the mosquito, the parasite and the host, man, give insight into the differences and the possibilities of control. Artemisinin derivatives can play an important role in malaria control, also in Africa. Without improvement of care which will require considerable investment and attention, the prospects are bleak.

Africa↗

Combinations of artemisinin and quinine for uncomplicated falciparum malaria: efficacy and pharmacodynamics.

Combinations of artemisinin and quinine for uncomplicated falciparum malaria were studied. A total of 268 patients were randomized to 7 days of quinine at 10 mg/kg of body weight three times a day (Q) or to artemisinin at 20 mg/kg of body weight followed by 3 (AQ3) or 5 (AQ5) days of quinine. Recrudescence rates were 16, 38, and 15% for the Q, AQ3, and AQ5 groups, respectively (P < 0.001). Recrudescence was associated with shorter parasite clearance time (PCT) and longer treatment after the blood smear had become negative (eradication time). However, classification of patients to outcome-recrudescence or radical cure-was correct in only 77% of patients. The population kinetics of the parasitemia was estimated with nonlinear mixed-effect models. Several models were tested, but the best model was a monoexponential decline of the parasitemia in which the mean parasite elimination half-life was shorter after artemisinin (5.1 h; 95% confidence interval [CI], 4.9 to 5.2 h) than after quinine (8.0 h [95% CI, 7.5 to 8.3 h]). Attempts to simulate the initial increase of the parasitemia did not result in better models with a biologically plausible interpretation. Recrudescence was associated with slower parasite clearance and a higher simulated terminal parasitemia (P(term)). The classification of patients to outcome groups based on P(term) was correct in 78% of patients. The data suggest that parasite strains with reduced sensitivity to quinine are prevalent in Vietnam, with slower parasite clearance and consequent recrudescence. A single dose of artemisinin induces rapid parasite reduction and lowers the value of P(term), but to prevent recrudescence, this should be followed by quinine for at least 3 days after parasite clearance, or 5 days in total.

Adolescent↗