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Biomedical subjects

L Rombo

Publications and source records attributed to L Rombo.

At least 19 recordsLinked to original sources

[Travellers to high-risk areas actively seek information on health hazards. A questionnaire study among Swedish charter tourists].

UNLABELLED: In order to study attitudes to travel-associated risks and adherence to advice, we sent a questionnaire to 2 x 2000 Swedish charter tourists who traveled to the Canary Islands, South East Asia or Gambia. METHODS: Questionnaires were answered either before the journey (n = 1249) or after return (n = 1223). RESULTS AND CONCLUSION: The travelers were usually well informed and followed the advice given. The opinion of the personnel who gave advice had a profound influence on which vaccines were taken. Those who more closely followed advice on what to eat and drink also reported diarrhea more frequently.

Attitude to Health↗

[Serious effects of chloroquine overdose. Prescribe the smallest possible dosage-packages and inform about the risks].

An increasing number of acute overdoses with chloroquine has been reported in Sweden--some with fatal outcome. This substance is clearly one of the most toxic pharmaceuticals on the Swedish market. Four cases are described. Travelling to the tropics has become very popular, and chloroquine is often given as a prophylactic antimalarial. This inexpensive drug is often prescribed in 100-tablet packages, and any surplus is often stored in the home. Awareness of toxicity is low among users and doctors in this country. Preventive measures are suggested.

Adolescent↗

Discrepancy in plasma melarsoprol concentrations between HPLC and bioassay methods in patients with T. gambiense sleeping sickness indicates that melarsoprol is metabolized.

OBJECTIVE: With the use of a specific high-performance liquid chromatography (HPLC) method and a bioassay which determines trypanocidal activity, concentrations of melarsoprol were assessed in plasma, urine and cerebrospinal fluid (CSF) from 8 patients with late-stage Trypanosoma gambiense sleeping sickness. The aim was to unravel to what extent the bioassay codetermines biologically active metabolites of melarsoprol. METHODS: Subjects were given one dose of melarsoprol i.v. per day for 4 days (1.2, 2.4, 3.0-3.6, 3.0-3.6 mg per kg b.w., respectively). Plasma samples were obtained before the first melarsoprol injection, immediately after and at 1 h, 24 h and 5 days after the 4th injection. Urine was collected before melarsoprol therapy and at 24 h after the 4th injection. CSF samples were taken once before treatment and at 24 h after the 4th injection. RESULTS: HPLC analyses showed that plasma concentrations immediately after the 4th injection varied from 2200 to 15,900 nmol/l; dropping to 0-1800 nmol/l at 1 h; and to undetectable levels at 24 h. In urine small amounts of melarsoprol were recovered. Melarsoprol could not be detected in CSF by HPLC. Immediately after injection, bioassay analyses showed plasma concentrations of the same magnitude as HPLC assays but at 1 h they were 4-65-fold higher than the levels assessed by HPLC. Even 24 h and 5 days after the 4th injection there was significant but decreasing activity. Urine levels were 40-260-fold higher than the measured HPLC concentrations, whereas there was low but detectable activity in CSF. CONCLUSION: Results indicate that melarsoprol is rapidly eliminated from plasma. The significant trypanocidal activity determined by bioassay and simultaneous low or undetectable levels of melarsoprol assayed by HPLC indicate that the compound is transformed into metabolites with parasiticidal activity.

Adolescent↗

Determination of melarsoprol in biological fluids by high-performance liquid chromatography and characterisation of two stereoisomers by nuclear magnetic resonance spectroscopy.

The analysis of melarsoprol in whole blood, plasma, urine and cerebrospinal fluid is described. Extraction was made with a mixture of chloroform and acetonitrile followed by back-extraction into phosphoric acid. A reversed-phase liquid chromatography system with ultraviolet detection was used. The relative standard deviation was 1% at concentrations around 10 mumol/l and 3-6% at the lower limit of determination (9 nmol/l in plasma, 93 nmol/l in whole blood, 45 nmol/l in urine and 10 nmol/l in cerebrospinal fluid). Melarsoprol is not a stable compound and samples to be stored for longer periods of time should be kept at -70 degrees C. Plasma samples can be stored at -20 degrees C for up to 2 months. Chromatography showed that melarsoprol contains two components. Using nuclear magnetic resonance spectroscopy the two components were shown to be diastereomers which slowly equilibrate by inversion of the configuration at the As atom.

Animals↗

Mefloquine tolerability during chemoprophylaxis: focus on adverse event assessments, stereochemistry and compliance.

This longitudinal study of travellers to Africa taking mefloquine (MQ) chemoprophylaxis aimed to quantify and assess non-serious adverse events (AE) occurring during short-term prophylaxis and relate these to concentrations of racemic MQ, its enantiomers and metabolite. A total of 420 volunteers (52% F) participated. AEs with some impact on activities were reported by 11.2% of participants including 7.9% of neurological/psychiatric symptoms. Women were more likely to report AEs (P = 0.02). The standardized questionnaires used showed more pathological indicators in travellers who reported subjective AE with significantly more dizziness, distress, sleep disturbances and a high total mood disturbance (TMD) in the AE group. There was, however, no significant performance deficit in computerized psychomotor tests in those experiencing AE. Furthermore, no significant differences were observed in enantiomer ratios, metabolite concentrations, or racemic MQ levels in participants with or without AEs suggesting that these factors are not the main predictors of mefloquine intolerability.

Adolescent↗

In vitro susceptibility of Plasmodium falciparum to quinine: relation to parasite density and drug distribution in culture fractions.

We have studied the importance of parasite density (2, 0.2, 0.02 and 0.002%) for the in vitro susceptibility of Plasmodium falciparum (F32 strain) to quinine. Shorter exposures (< or = 48 hours) only briefly inhibited parasites in wells with the highest initial density. Parasites reappeared after 3-5.5 days in wells with intermediate (0.2 and 0.02%) and lowest density (0.002%). Longer exposures (> or = 72 hours), however, inhibited them for much longer periods and parasites did not reappear in most of the wells with the lowest density during the 28 days of follow-up. The mean multiplication rate following reappearance was tenfold per parasite schizogony cycle. The mean elimination rate per schizogony cycle was calculated to be 99.91%. The elimination and multiplication rates were not correlated to initial parasite density. The mean ratio between quinine concentrations in erythrocytes and medium was 3.6 regardless of quinine concentrations and presence of parasites. Mean quinine-free fractions of 36 and 67% were found from total concentrations of 0.33 and 10.4 mumol/l. We conclude that initial parasite density determines the time to reappearance of parasites following quinine exposure while the elimination and multiplication rates are independent of the initial parasite density, and that quinine protein binding is concentration-dependent in vitro and lower than during treatment.

Animals↗

Pharmacokinetics and adverse reactions after a single dose of pentamidine in patients with Trypanosoma gambiense sleeping sickness.

1. Plasma concentrations of pentamidine were measured up to 1-8 months after a single 2 h i.v. infusion of 3.0 to 4.8 mg kg-1 pentamidine isethionate in 11 patients with late stage Trypanosoma gambiense sleeping sickness. 2. Maximum plasma drug concentrations varied between 713 and 2461 nmol 1-1. After termination of infusion, a rapid distribution phase over 10 min was followed by a slower distribution phase and an elimination phase prolonged over weeks to months. 3. The 'terminal' elimination rate constant could be determined in six patients and subsequent kinetic calculations showed a three to fourfold variation in plasma clearance and 'terminal' half-life (median 1126 (range 553-2036) ml min-1 and 265 (107-446) h, respectively). The median apparent volume of distribution (Vss) was 11,850 1. Renal clearance accounted for a median of 11% of total plasma clearance, indicating that metabolism is a major route of pentamidine elimination in man. 4. Side effects were few and mild and a slight or moderate decrease in blood pressure was the most common registered adverse reaction observed in four subjects. 5. The prolonged elimination of pentamidine seems inconsistent with the present recommended dosage regimen of pentamidine for treatment of trypanosomiasis of 7 to 10 parenteral doses given once daily or every second day.

Adult↗