Protection against the toxicity of microcystin-LR and cylindrospermopsin in Artemia salina and Daphnia spp. by pre-treatment with cyanobacterial lipopolysaccharide (LPS)

Purified cyanobacterial lipopolysaccharide (LPS) was not acutely toxic to three aquatic invertebrates (Artemia salina, Daphnia magna and Daphnia galeata) in immersion trials. However, pre-exposure (24 h) to 2 ng mL⁻¹ LPS increased the LC₅₀ of microcystin-LR significantly in all 3 species. Similar results were observed with A. salina pre-treated with the same concentration of cyanobacterial LPS and subsequently exposed to cylindrospermopsin, increasing the LC₅₀ by 8. The findings indicate the need to include exposures to defined combinations of cyanotoxins, and in defined sequences, to understand the contributions of individual cyanotoxins in accounting for cyanobacterial toxicity to invertebrates in natural aquatic environments.     

Outcome of aneurysmal subarachnoid hemorrhage in patients 66 years of age and older

The outcome at three months after aneurysmal SAH in a group of older patients and a group of younger patients is compared. The patients were admitted within 72 hours of their SAH. Of 61 patients 66 years of age and older, comprising 13% of the whole patient group, 52% died, 12% remained dependent and 36% became independent. In the younger group, 55% had an independent outcome (p less than 0.01). In contrast to what we expected in the older patient group, not extracranial, but intracranial events (re-bleeds, infarcts, hydrocephalus) were by far the most frequent cause of deterioration.     

Contact lens fitting following corneal graft surgery

Contact lens fitting may be required following keratoplasty for either optical or thera‐peutic reasons. Optical indications for contact lens fitting include the correction of irregular astigmatism, high regular astigmatism, anisometropia and secondary aniseikonia, as well as simple ametropia, where the patient desires to wear contact lenses in preference to spectacles. Therapeutic lenses are not routinely fitted following kerate plasty, although this management is advised in certain cases, such as when there are protruding sutures or epithelial healing is impaired. Designing a contact lens for a patient who has undergone keratoplasty will require the practitioner to carefully assess all the relevant features of the corneal graft. In this regard, there are many factors that need to be considered including the diameter of the graft zone, the topographical relationship between the host cornea and donor cornea, the corneal (graft) toricity and the location of the graft. Special designs, such as reverse geometry lenses, or more complex contact lens modalities, such as piggyback contact lens systems, may be required to achieve success in fitting.     

Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers.

Siberian ginseng ([SG]; Eleutherococcus senticosus) is a commonly used herbal preparation. The objective of this study was to assess in normal volunteers (n = 12) the influence of a standardized SG extract on the activity of cytochrome P450 CYP2D6 and 3A4. Probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again following treatment with SG (1 x 485 mg twice daily) for 14 days. Urinary concentrations of dextromethorphan and dextorphan were quantified, and dextromethorphan metabolic ratios (DMRs) were determined at baseline and after SG treatment. Likewise, plasma samples were collected (0-60 h) for alprazolam pharmacokinetics at baseline and after SG treatment to assess effects on CYP3A4 activity. Validated high performance liquid chromatography methods were used to quantify all compounds and relevant metabolites. There were no statistically significant differences between pre- and post-SG treatment DMRs indicating a lack of effect on CYP2D6 (P > 0.05). For alprazolam there also were no significant differences in the pharmacokinetic parameters determined by noncompartmental modeling (C(max), T(max), area under the curve, half-life of elimination) indicating that SG does not significantly induce or inhibit CYP3A4 (P > 0.05). Our results indicate that standardized extracts of SG at generally recommended doses for over-the-counter use are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination.     

Histomorphometric features of hydatidiform moles in early pregnancy: relationship to detectability by ultrasound examination.

OBJECTIVE: The majority of partial (PHM) and complete (CHM) hydatidiform moles are diagnosed in early pregnancy. About half are identified as molar on ultrasonographic examination prior to evacuation. It is uncertain whether unsuspected cases represent an intrinsically different molar phenotype or are simply dependant on sonographer expertise. We measured a microscopic parameter, average villus diameter, of evacuated PHMs and CHMs to ascertain the cause of non-detection on ultrasound. METHODS: Fifty-four molar pregnancies were examined from the files of the Trophoblastic Disease Unit, in which results of an ultrasound examination prior to evacuation were known. In each, the average cross-sectional diameter of the largest 10 villi was recorded. Maximum villus diameters were compared between gestational age groups (<14 weeks and >or=14 weeks), and ultrasound detection groups (detected (d) and not detected (nd)). RESULTS: The average maximum villus diameter of the largest hydropic villi was significantly less in the first trimester for both PHMs and CHMs that were undetected by ultrasound examination compared to those identified as molar sonographically (P<0.001 and P<0.001, respectively). There was no significant difference in the maximum villus diameter between PHMs and CHMs that were not detected sonographically in the first trimester (P=0.44). Beyond 14 weeks of gestation, there was no significant difference between PHMs detected and undetected sonographically (P=0.88). CONCLUSION: The average diameter of the largest, most hydropic villi, is significantly greater in cases of PHMs and CHMs detected by ultrasound examination in the first trimester compared to that of those not detected sonographically, but beyond 14 weeks such differences are minimal. These findings suggest that, although sonographer expertise could potentially increase ultrasound detection rates somewhat for PHMs and CHMs, a significant proportion of cases demonstrate minimal hydropic change in the first trimester and are therefore likely to remain unidentifiable by ultrasound examination prior to evacuation, even with improved sonographer expertise.     

Evaluation of tetracycline on theophylline disposition in patients with chronic obstructive airways disease

Theophylline is a commonly used bronchodilator in the treatment of chronic obstructive airways disease (COAD) with a narrow therapeutic range of 10 to 20 micrograms/ml. Patients with COAD frequently receive concomitant antibiotic therapy for respiratory infections. This study evaluated the effect of tetracycline therapy on theophylline disposition in adults with COAD. Six males (five nonsmokers) with obstructive ventilatory defects were studied in two phases: control, after receiving sustained-release theophylline in the same dosage regimen for four days, and treatment, after receiving tetracycline 250 mg po qid for five days in addition to theophylline. During each phase, 10 blood samples were obtained over one dosing interval and analyzed for theophylline content. The following pharmacokinetic parameters were calculated: Cmin, Cmax, Css, percentage fluctuation and Cl. Differences for each value were tested as paired data with Student's two-tailed t-test. When all patients were evaluated, the only statistically significant difference was for Cmax. However, when the five nonsmokers were evaluated separately, differences were observed for Css (micrograms/ml; mean +/- SD) 9.3 +/- 3.0, control, and 10.6 +/- 3.8, treatment (p = 0.041); and for Cl [( ml/h]/kg; mean +/- SD) 49.0 +/- 11.1, control, and 43.6 +/- 10.2, treatment (p = 0.019). This study demonstrates that tetracycline may weakly inhibit theophylline clearance in nonsmoking adults with COAD.