Comparative efficacy of a single 400 mg dose of albendazole or mebendazole in the treatment of nematode infections in children

The relative efficacy of a single 400 mg dose of albendazole or mebendazole in the treatment of nematode infections was assessed in 2- to 9-year-old children living in two different Bolivian rural communities. Both agents were equally very effective (100% cure rate) in treating ascariasis. Albendazole was clearly more active than mebendazole against hookworm infections, both in terms of egg reduction rate (92.8% vs. 62.4%) and cure rate (81.8% vs. 17.2%). As far as trichuriasis is concerned, albendazole produced a higher egg reduction rate than mebendazole (45.7% vs 15%), but a lower cure rate (33.3% vs 60%). Both drugs were well tolerated.     

Pharmacokinetics of a single dose of teicoplanin in burn patients

Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients. This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns. Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%). Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h). Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h). The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration. A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.     

Time of peak drug concentration after a single dose and a dose at steady state

The time of peak concentration after administration of oral drug is an often quoted and used pharmacokinetic parameter. It is not well appreciated, however, that the peak times after a single dose and a dose at steady state during a multiple administration regimen can differ significantly. This article derives the mathematical relationships that determine how a peak time at steady state differs from that after a single or first dose. These relationships are then evaluated using three different approaches: 1) graphic simulations of time courses of drug concentration for three hypothetical drugs; 2) comparisons of predicted and observed peak times using examples from the literature; and 3) comparisons of predicted and simulated peak times based on different sampling schedules for three hypothetical drugs. The key finding is that peak times after a dose at steady state can occur considerably earlier after administration than after a single dose. However, the manner by which peak times are usually determined, that is, the sampling time corresponding to the highest measured drug concentration, imposes significant limitations on the usefulness of this parameter.     

High effectiveness and safety of one-week antibiotic regimen in Helicobacter pylori eradication

Forty-three sporadic gastric cancers were analyzed with regard to whether mutations of simple repeated sequences in the transforming growth factor beta type II receptor (TbetaR-II) gene are associated with microsatellite instability (MSI) and gastric carcinogenesis. In 12 of the 43 cancers (28%), MSI was observed at least at 1 of the 2 microsatellite loci. Frameshift mutations of the TbetaR-II gene, all of which were 1 base deletion of 10 adenine repeats, were detected in 3 of 6 cancers, with MSI at 2 loci. However, mutations were not detected in 6 cancers, with MSI only at 1 locus and 31 cancers without MSI. Moreover, microanalysis in these cases revealed that the mutant-type alleles of TbetaR-II were invariably common in different areas within the tumor, in contrast to the markedly variable alleles of microsatellite loci. Our results suggest that frameshift mutation of the TbetaR-II gene may be a critical event associated with MSI and may contribute to carcinogenesis of the stomach. One of the possible mechanisms of escape from growth control by TGFbeta during gastric carcinogenesis could involve frameshift mutations of the TbetaR-II gene caused by DNA replication errors.     

Community-acquired pneumonia in adults: initial antibiotic therapy

One of the current goals in vaccine development is the noninvasive administration of protective antigens via mucosal surfaces. In this context, the gut-associated lymphoid tissues have already been extensively explored. Vaccination via the nasal route has only recently been the focus of intensive investigation, and no live vector specifically designed for the respiratory mucosa is yet available. In this study we show that intranasal administration of the recombinant Bordetella pertussis BPGR60, producing the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) protective antigen fused to filamentous hemagglutinin, induces priming in mice for the production of serum antibodies. In addition to significant levels of anti-Sm28GST immunoglobulin A (IgA) antibodies, high levels of anti-Sm28GST serum antibodies were obtained after intranasal boost with the purified antigen or infection with S. mansoni following intranasal priming with BPGR60. These antibodies were of the IgG1, IgG2a, and IgG2b isotypes, suggesting a mixed immune response. No priming was observed in animals that had received nonrecombinant B. pertussis or purified Sm28GST, indicating specific priming by BPGR60. This priming was also evident in immune protection against S. mansoni challenge. Significant protection against worm burden and egg output was obtained in mice primed with BPGR60 and intranasally boosted with purified Sm28GST. A lower but still significant degree of protection against egg output was also obtained in mice infected with a single dose of BPGR60. These results indicate that intranasal administration of recombinant B. pertussis can prime for serum antibody responses against a foreign antigen and for heterologous protection.     

The use of a GnRH antagonist (Cetrorelix) in a single dose protocol in IVF-embryo transfer: a dose finding study of 3 versus 2 mg

New gonadotrophin-releasing hormone (GnRH) antagonists, which allow suppression of luteinizing hormone (LH) surges, have recently become available. We compared in this study the results of a single administration of 3 versus 2 mg Cetrorelix in 65 patients undergoing ovarian stimulation and in-vitro fertilization (IVF). The GnRH antagonist (Cetrorelix) was non-randomly administered at a dose of 3 mg (34 patients) or 2 mg (32 patients) on day 8 of the stimulation cycle. In the case of slow follicular development, the injection was delayed until oestradiol reached 400 pg/ml. No difference was observed in the decrease in LH and in oestradiol secretion between the 3 and the 2 mg groups, but the LH secretion was suppressed for a shorter time in the 2 mg group. No LH surge was observed in the 3 mg group, while one surge (3%) and one significant rise in LH were observed in the 2 mg group. No significant difference was observed in IVF results in the two groups of patients. This study demonstrates that a single injection of 3 or 2 mg successfully prevents LH surges for at least 3 days in all the patients treated. The LH rises in the 2 mg group led us to choose the 3 mg dose as a safer dose in our single administration protocol.     

The treatment of non-gonococcal urethritis with single dose oral azithromycin

In an uncontrolled study, the efficacy of azithromycin in the treatment of non-gonococcal urethritis was assessed in 41 male patients aged between 20 and 40 years with a mean age of 27 +/- 5 years. Clinical and microbiological diagnosis confirmed that 28 men were found positive for Chlamydia trachomatis, 10 for Ureaplasma urealyticum and three for both C. trachomatis and U. urealyticum. All patients received 1 g azithromycin orally (four 250 mg capsules). The length of time between the treatment and following visits were 7-10 days and 14-21 days for second and third visits, respectively. Complete eradication was achieved in 27 out of 41 patients. Of the remaining 14, six were found positive for C. trachomatis and were excluded as they did not return for the follow-up visit, one patient did not achieve complete eradication, one patient infected with both C. trachomatis and U. urealyticum failed to achieve complete eradication, and six patients infected with U. urealyticum failed to be completely cured. No adverse effects were reported in any patient. Single dose administration of 1 g azithromycin appears to be an effective and well-tolerated treatment for chlamydial urethritis and an advantage in terms of patient compliance.     

Anticoagulation in hemodialysis with a single dose of low molecular weight heparin

The aim of this work was to compare the benefits and problems of low molecular weight heparin use in chronic hemodialysis, compared to conventional heparin. We studied 35 patients that received low molecular weight heparin (Enoxaparine, molecular weight 4000) during 115 consecutive hemodialysis procedures and conventional heparin during the subsequent 35 procedures. We assess the heparin dose, partial thromboplastin time before dialysis and at 3 and 120 min during the procedure, arterio-venous fistula compression time, clot formation in the circuit and residual volume of filters. Median total dose of conventional heparin was 6289 U (range 3000-10000) compared to 5555 U (range 2000-8000) of low molecular weight heparin. When the dose was calculated per kg of body weight, it was lower for low molecular weight heparin than for conventional heparin (87.8 U (range 33-100) vs 100 U (range 50-176)). Partial thromboplastin time achieved was lower with low molecular weight heparin, compared with conventional heparin, at 3 (64.26 vs 125.2 sec) and 120 min (39.1 vs 84.45 sec). Clot formation, arteriovenous fistula compression time and residual volume of filters were similar for both types of heparin. It is concluded that a single dose of low molecular weight heparin simplifies anticoagulation during hemodialysis, modifies less the partial thromboplastin time and does not alter filter re-utilization.     

The assessment of residual effects of a single dose of diazepam on visually-defined EEG patterns

Patients with medically intractable trigeminal neuralgia characterized by paroxysmal, triggered, trigeminally distributed pain are excellent candidates for neurosurgical intervention, which can not only relieve the pain of trigeminal neuralgia, but also eliminate the unpleasant side effects of medicines used to treat it. The two major neurosurgical choices are percutaneous denervation and microvascular decompression (MVD). Percutaneous denervation is done best when the surgeon has available radiofrequency and glycerol and uses one, the other, or both depending on technical circumstances that pertain to each patient. The percutaneous denervation is less likely than MVD to cause death, stroke, facial weakness, or hearing loss, but more likely to be associated with recurrence or dysesthesias. Patients with multiple sclerosis, medical illness, or who are elderly are much better candidates for percutaneous denervation. For any patient, a number of other factors also must be considered before deciding on a particular procedure. These include response to previous interventions, ability to tolerate carbamazepine, risk tolerance for various complications, preference regarding duration of hospital stay and postoperative recovery, presence of pain outside the trigeminal distribution, and findings on a high resolution magnetic resonance imaging (MRI) scan.     

Urinary excretion and bactericidal activities of a single oral dose of 400 milligrams of fleroxacin versus a single oral dose of 800 milligrams of pefloxacin in healthy volunteers

Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin, N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects' urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 microgram/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 micrograms/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true for Enterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.     

Attentional effects of single dose triazolam

1. While the effects of benzodiazepines on human memory have been extensively studied little is known about the effects of these agents on attentional processes. The authors studied the effects of a single dose of triazolam on selective visual-spatial attention using a double blind, placebo controlled design. 2. In each of 2 sessions 12 normal volunteers ingested either 0.25 mg of triazolam or placebo. Attentional performance was evaluated using two versions of the covert orienting paradigm which measured automatic (exogenous) and controlled (endogenous) aspects of attentional orienting, respectively. 3. Triazolam selectively modified performance on automatic orienting to exogenous cues. Specifically, triazolam increased the facilitation of target detection seen at shorter (150 msec) SOA's. This may indicate an increase in facilitation and a reduction in inhibition or a slowing of the time course of the biphasic attentional effect normally resulting from exogenous cuing. 4. These results indicate the importance of using experimental paradigms which effectively dissociate endogenous and exogenous mechanisms of spatial orienting in studies evaluating the effects of pharmacological agents on visual-spatial attention.     

The efficacy of computer-provided reading treatment for chronic aphasic adults

We examined the effects of computer-provided reading activities on language performance in chronic aphasic patients. Fifty-five aphasic adults were assigned randomly to one of three conditions: computer reading treatment, computer stimulation, or no treatment. Subjects in the computer groups used computer 3 hours each week for 26 weeks. Computer reading treatment software consisted of visual matching and reading comprehension tasks. Computer stimulation software consisted of nonverbal games and cognitive rehabilitation tasks. Language measures were administered to all subjects at entry and after 3 and 6 months. Significant improvement over the 26 weeks occurred on five language measures for the computer reading treatment group, on one language measure for the computer stimulation group, and on none of the language measures for the no-treatment group. The computer reading treatment group displayed significantly more improvement on the Porch Index of Communicative Ability "Overall" and "Verbal" modality percentiles and on the Western Aphasia Battery Aphasia "Quotient" and "Repetition" subtest than the other two groups. The results suggest that (a) computerized reading treatment can be administered with minimal assistance from a clinician, (b) improvement on the computerized reading treatment tasks generalized to non-computer language performance, (c) improvement resulted from the language content of the software and not stimulation provided by a computer, and (d) the computerized reading treatment we provided to chronic aphasic patients was efficacious.     

Haloperidol and reduced haloperidol plasma concentrations after a loading dose regimen with haloperidol decanoate

1. Haloperidol and reduced haloperidol plasma levels were measured in schizophrenic patients who received both oral (10 mg, N=16 and 20 mg, N=4) and depot haloperidol treatment 2. Patients were of Asian ethnicity and were safely and effectively converted from oral to depot therapy using a loading dose regimen using a 100 mg weekly injection interval for 4 weeks, biweekly for one month and then monthly. 3. Significant correlations were found for plasma haloperidol and reduced haloperidol levels and reduced haloperidol/haloperidol ratios between oral and depot therapy in these non-smoking patients. 4. A loading dose regimen is needed due to the long elimination half-life of decanoate of 26 days otherwise steady-state condition will not occur until 34 months of therapy. 5. Patients were maintained on monthly depot treatment for 40 weeks after the loading dose regimen and only one patient relapsed during treatment despite dosage increases. 6. The formation of reduced haloperidol remained consistent for oral and depot haloperidol treatment.     

Sustained-release of levodopa: single dose study of a new formulation

Motor fluctuations and dyskinesias in Parkinsonian patients may be at least partially due to fluctuations of levodopa plasma concentrations. Sustained-release (SR) formulations of levodopa may present a promising, effective solution of this problem. Therefore we performed a 4-fold, cross-over double-blind trial with a new SR preparation, tested in healthy volunteers (Gerlach et al., 1988) before, in 12 Parkinsonian subjects. Two different dosages of the pure new levodopa SR-preparation, a composition of 70% SR and 30% levodopa immediate release (IR) and a conventional IR levodopa preparation were compared by their pharmacokinetic behaviour and their clinical effects. The relative bioavailability of levodopa in plasma was 69% for the combination of SR and IR levodopa release, for the pure SR formulations (100 mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa. In contrast to the conventional IR formulation the pharmacokinetic behaviour of the SR preparations showed no initial sharp peak, but more continuous and longer maintaining plasma concentrations of levodopa. Due to the small numbers of cases and the missing homogenity of the selected patients no statistical significant differences between the four preparations regarding the clinical response were observed. But the described pharmacokinetic behaviour gives hope, that these newly developed SR-preparations may lead to progress in the treatment of Parkinson's disease (prolongation of dosage intervals, reduction of motor fluctuations).     

Intraoperative blood salvage in children and young adults undergoing spinal surgery with predeposited autologous blood: efficacy and cost effectiveness

We conducted a retrospective review of 155 spinal operations at our institution to determine the efficacy of intraoperative salvage. Addition of intraoperative salvage had little effect on the success of a preoperative autologous donation program. Only patients with operative blood loss > 2,000 ml (12% of patients) benefited from this expensive source of autologous blood. The technique tended to be most effective in children aged 16-18 years. Use of intraoperative salvage for all pediatric spinal procedures is neither necessary nor cost effective.     

Pharmacokinetics of fusidic acid after a single dose of a new paediatric suspension

Cell proliferation in response to growth factors is mediated by specific high affinity receptors. Ligand-binding by receptors of the protein tyrosine kinase family results in the stimulation of several intracellular signal transduction pathways. Key signalling enzymes are recruited to the plasma membrane through the formation of stable complexes with activated receptors. These interactions are mediated by the conserved, non-catalytic SH2 domains present in the signalling molecules, which bind with high affinity and specificity to tyrosine-phosphorylated sequences on the receptors. The assembly of enzyme complexes is emerging as a major mechanism of signal transduction and may regulate the pleiotropic effects of growth factors.