Saved by the pump: Two successful resuscitations utilising emergency department-initiated extracorporeal cardiopulmonary resuscitation in South Africa.

Extracorporeal life support is the utilisation of advanced techniques to sustain circulatory and/or ventilatory functions in critically ill patients when standard therapies fail. It is well established in developed countries. There is increasing literature supporting its application in refractory cardiac arrest with a potential reversible cause, a procedure also known as extracorporeal cardiopulmonary resuscitation (eCPR). Two cases where eCPR was successfully utilised in a busy (>30 000 visits per year) private South African emergency department are described here, the first such cases to be reported on the African continent. The first patient had a life-threatening cardiac arrhythmia due to toxin ingestion, and the second a refractory ventricular fibrillation due to acute myocardial infarction. In both these cases the cardiac arrest was witnessed, occurred in the emergency department, and failed to respond to standard advanced resuscitative measures. Both the patients were discharged neurologically intact. Although it is effective, the benefit of this advanced method of resuscitation in a low- to middle-income country is debated.

Dieback and decline pathogens of olive trees in South Africa.

Trunk disease fungal pathogens reduce olive production globally by causing cankers, dieback, and other decline-related symptoms on olive trees. Very few fungi have been reported in association with olive dieback and decline in South Africa. Many of the fungal species reported from symptomatic olive trees in other countries have broad host ranges and are known to occur on other woody host plants in the Western Cape province, the main olive production region of South Africa. This survey investigated the diversity of fungi and symptoms associated with olive dieback and decline in South Africa. Isolations were made from internal wood symptoms of 145 European and 42 wild olive trees sampled in 10 and 9 districts, respectively. A total of 99 taxa were identified among 440 fungal isolates using combinations of morphological and molecular techniques. A new species of Pseudophaeomoniella, P. globosa, had the highest incidence, being recovered from 42.8 % of European and 54.8 % of wild olive samples. This species was recovered from 9 of the 10 districts where European olive trees were sampled and from all districts where wild olive trees were sampled. Members of the Phaeomoniellales (mainly P. globosa) were the most prevalent fungi in five of the seven symptom types considered, the only exceptions being twig dieback, where members of the Botryosphaeriaceae were more common, and soft/white rot where only Basidiomycota were recovered. Several of the species identified are known as pathogens of olives or other woody crops either in South Africa or elsewhere in the world, including species of Neofusicoccum, Phaeoacremonium, and Pleurostoma richardsiae. However, 81 of the 99 taxa identified have not previously been recorded on olive trees and have unknown interactions with this host. These taxa include one new genus and several putative new species, of which four are formally described as Celerioriella umnquma sp. nov., Pseudophaeomoniella globosa sp. nov., Vredendaliella oleae gen. & sp. nov., and Xenocylindrosporium margaritarum sp. nov.

Hutchinson's sign as a marker of ocular involvement in HIV-positive patients with herpes zoster ophthalmicus.

BACKGROUND: A positive Hutchinson's sign indicates an increased risk of ocular involvement in herpes zoster ophthalmicus (HZO). We examined the sensitivity of Hutchinson's sign as an indicator of ocular involvement in a consecutive series of patients presenting with HZO. METHODS: We conducted a descriptive observational prospective study of patients > or =18 years old presenting with HZO and consenting to pre-and post-test counselling and HIV and CD4 testing. A full ophthalmological examination focused on the extent of ocular involvement, and the presence of Hutchinson's sign was confirmed by two clinicians. RESULTS: Thirty-three patients were enrolled; 29 were HIV positive, of whom 18 (62%) had not been diagnosed with HIV prior to enrollment. Of the 29 HIV-positive patients, 21 (72%) were Hutchinson's sign positive (HSP), all of whom had intra-ocular involvement (95% confidence interval 88 - 100%). Of the 8 HIV-positive, Hutchinson's sign-negative (HSN) patients, 4 did and 4 did not display intra-ocular involvement. Neither the mean CD4 count nor the average age in the HSP group differed significantly from the HSN group. CONCLUSION: We confirmed that a Hutchinson's sign- and HIV-positive patient with HZO has a very high positive predictive value for intra-ocular involvement. Neither age nor CD4 count had predictive value for ocular involvement. Young adults presenting with HZO should be suspected of having HIV, and HIV-positive patients with HZO but HSN may still have ocular involvement. All patients with HZO should be seen by an ophthalmologist.

Comparable spirometric efficacy of tiotropium compared with salmeterol plus fluticasone in patients with COPD: a pilot study.

BACKGROUND: International guidelines recommend the long-acting anticholinergic, tiotropium, or long-acting beta 2-agonists as maintenance therapy in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The efficacy of long-acting beta(2)-agonists combined with inhaled corticosteroids (ICS) in the treatment of COPD has also been confirmed for severe and very severe COPD, but data comparing tiotropium with the combination of a long-acting beta 2-agonist and an ICS are lacking. METHODS: This 6-week multicentre, randomised, double-blind, triple-dummy pilot study compared the bronchodilator effects of tiotropium 18 microg once daily (n=56) vs. the combination of salmeterol 50 microg plus fluticasone 250 microg twice daily (n=51) in patients with moderate-to-very severe COPD. Serial spirometry was performed over 12h after 6 weeks of treatment. The primary endpoint was forced expiratory volume in 1s (FEV1) area under the curve from 0 to 12h (AUC0-12h) on Day 43. RESULTS: Randomization failed to provide treatment groups with comparable baseline characteristics for smoking history, current smokers, duration of COPD, FEV1, forced vital capacity (FVC) and reversibility. Mean+/-SD FEV1 was 1.31+/-0.47 l in the tiotropium group vs. 1.46+/-0.53 l in the salmeterol plus fluticasone group. Fewer patients in the tiotropium showed a 12% and 200 ml acute increase to short-acting bronchodilators at baseline. However, treatment with tiotropium alone resulted in comparable bronchodilation compared with salmeterol plus fluticasone, as measured by all the spirometric parameters at the end of the 6-week study period. FEV1 AUC0-12h was 1.55+/-0.03 l in the tiotropium group vs. 1.57+/-0.04 l in the salmeterol plus fluticasone groups (p=0.63). Trough (predose) FEV1 was 1.54+/-0.03 l in the tiotropium group vs. 1.46+/-0.03 l in the combination group (p=0.07), and peak FEV(1) was 1.68+/-0.04 l vs. 1.66+/-0.04 l, respectively, (p=0.77). FVC AUC0-12h, trough and peak were also comparable between groups at study end (p>0.05, for all). Further, rescue salbutamol use was similar in the tiotropium and combination groups and both treatment regimens were well tolerated. CONCLUSIONS: Six weeks of treatment with tiotropium resulted in comparable bronchodilation compared with salmeterol plus fluticasone in patients with moderate-to-very severe COPD, despite tiotropium patients having lower lung function and fewer patients considered reversible at baseline. The results of this pilot study will aid planning for further large-scale comparative studies.

Biocatalysis of nitro substituted styrene oxides by non-conventional yeasts.

Yeast strains (410) from more than 45 different genera were screened for the enantioselective hydrolysis of nitro substituted styrene oxides. These strains included 262 yeasts with known epoxides hydrolase activity for various other epoxides. Epoxide hydrolase activity for p-nitrostyrene oxide (pNSO) (177 strains) and m-nitrostyrene oxide (mNSO) (148 strains) was widespread in the yeasts, while activity for o-nitrostyrene oxide (oNSO) was less ubiquitous (22 strains). The strains that displayed enantioselectivity in the hydrolysis of one or more of the nitro substituted styrene oxides (35 strains) were also screened against styrene oxide (SO). Rhodosporidium toruloides UOFS Y-0471 displayed the highest enantioselectivity for pNSO (ee 55%, yield 35%) while Rhodotorula glutinis UOFS Y-0653 displayed the highest enantioselectivity for mNSO (ee > 98%, yield 29%), oNSO (ee 39%, yield 19%) and SO (ee > 98%, yield 19%). (R)-Styrene oxide was preferentially hydrolysed to the corresponding (R)-diol with retention of configuration at the stereogenic centre. In the case of the nitro substituted styrene oxides the absolute configurations of the remaining epoxides and the formed diols were not established.

Characterization of inositolpolyphosphate binding to myocardial membranes.

Although it is well-accepted that the phosphatidylinositol signalling transduction pathway, producing inositol-1,4,5-P3 (InsP3) and inositol-1,3,4,5-P4 (InsP4) as second messengers, functions in heart muscle, virtually nothing is known about the roles of the higher inositol polyphosphates such as inositolhexakisphosphate (InsP6). This study demonstrates that InsP6 has the ability to bind intracellularly, with different binding characteristics, to different myocardial membranes. Binding to purified sarcoplasmic reticulum (SR) membranes, purified sarcolemmal (SL) membranes as well as to viable mitochondria were characterized. Binding to all these membranes display high as well as low affinity binding sites, with differing affinities. Kd values of binding to SR were 32 and 383 nM, to SL 61 and 1312 nM, while those of mitochondrial binding were 230 and 2200 nM respectively. InsP4 binding was also investigated and displayed the following characteristics: to SR, one low affinity binding site (Kd = 203 nM) and to SL, a high as well as a low affinity binding site with Kd values of 41 and 2075 nM respectively. Presence of InsP3, the second messenger for SR calcium release, at concentrations of 1 nM, elevated the binding of InsP4 to SR and SL by a mean of 30% and 20% respectively. Fractionation of SR and SL membranes on sucrose density gradients, after solubilization with CHAPS, indicated that InsP6 bound to two separate protein peaks in both these membranes, while InsP4 bound to only one. In SR membranes, InsP4 bound preferentially to a protein separating at high sucrose density while it bound to a protein separating at low sucrose density in SL membranes.

Relative bioavailability of four controlled-release nifedipine products.

Four controlled-release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple-dose, randomized, crossover study to determine the relative bioavailability of two 10 mg controlled-release nifedipine tablets (Adalat Retard, Bayer), administered 12 hourly, and one 20 mg controlled-release nifedipine tablet (Adalat Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple-dose, randomized, three-period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro-intestinal therapeutic system (GITS) tablets (Adalat XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled-release tablet (Adalat Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled-release characteristics of the different formulations, were collected. Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat XL) have better controlled-release properties than the Adalat Retard product, and are suitable for once-a-day administration.

Hydroxy long-chain fatty acids in fungi.

Hydroxy long-chain fatty acids occur widely in animals and plants and have important physiological activities in these eukaryotes. There are indications that these compounds are also common and important in fungi. The occurrence of hydroxy-polyunsaturated fatty acids (hydroxy-PUFAs) is of biotechnological importance, because these compounds are potentially high-value lipid products with medical applications. This review pays particular attention to the production of hydroxy-PUFAs by yeasts and other fungi. Hydroxy-PUFAs derived from lipoxygenase activity appear to be present in most fungi, while hydroxy-PUFAs from cyclooxygenase activity (i.e. prostaglandins) have mainly been implicated in the Oomycota and in yeasts from the genus Dipodascopsis. The occurrence of other hydroxy long-chain fatty acids in fungi is also discussed briefly; these include hydroxy fatty acids that are generally associated with cytochrome P-450 monooxygenase activity (i.e. terminal and sub-terminal hydroxy acids and diols derived from the corresponding epoxides) as well as 2-hydroxy-fatty acids and 3-hydroxy-fatty acids.

Steady-state pharmacokinetics of phentermine extended-release capsules.

Twenty-one healthy, caucasian, male volunteers completed this randomized single blind, multiple-dose, crossover bioavailability study during which either phentermine HCl capsules (Minobese Forte, reference product) or phentermine base capsules (Duromine, test product) were ingested once daily for 14 days. A washout period of 14 days was allowed between the two treatment phases. On profile days (day 14 of each treatment phase) subjects remained recumbent for 24 hours after drug administration. Serial venous blood samples were drawn over the 24 hour dosing interval for plasma phentermine assay by gas chromatography. The 90% confidence intervals for the "test/reference" mean ratios of the pharmacokinetic variables Cmax,norm, Cmin,norm, AUCnorm (normalized for difference in the dose of phentermine base), %PTF and T75% Cmax, all fell within the bioequivalence range of 80% to 125%. With the aid of trough plasma phentermine concentrations, it was established that steady-state was reached after 14 days of once daily administration of either product. Adverse events experienced on both treatments included prolonged or recurrent episodes of insomnia, nausea, headache, dry mouth and dizziness. No clinically relevant changes in clinical chemistry or hematology variables occurred during the study.

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout.

The objectives of this study were to establish if, and to what extent, benzbromarone affects allopurinol/oxypurinol kinetics, and to compare the uric acid lowering capabilities of Allomaron (allopurinol 100 mg plus benzbromarone 20 mg) with the effects of allopurinol alone in patients with confirmed gout. We studied 14 adult men in an open randomized cross-over study. After a 14 day run-in period with Zyloprim (2 x 100 mg allopurinol tablets in the morning), the patients were randomly allocated to morning doses of either Allomaron (2 tablets) or Zyloprim (2 tablets). Seven days later cross-over was effected and the alternative treatment was taken for a further 7 days. On days 7 and 14 the patients came into hospital and venous blood samples were taken over 24 h for allopurinol and oxypurinol assays by HPLC. Serum uric acid was determined on days -14, 1, 7, and 14. Benzbromarone lowered plasma oxypurinol concentrations (Allomaron/Zyloprim mean ratio of AUC0-->24 was 59%; 95% confidence interval 54-64%), but did not affect plasma allopurinol concentrations. Despite this pharmacokinetic interaction of benzbromarone with allopurinol, resulting in lower plasma concentrations of oxypurinol, Allomaron was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone.

Evidence for, and taxonomic value of, an arachidonic acid cascade in the Lipomycetaceae.

By using specific inhibitors of the lipoxygenase and cyclo-oxygenase pathways, arachidonic acid metabolites with similar sensitivities towards these inhibitors as in humans, were detected in Dipodascopsis uninucleata. The taxonomic value of aspirin sensitive arachidonic acid metabolites in the Lipomycetaceae was next assessed. No metabolites of which the production is inhibited by aspirin were detected in strains representing the following species: Lipomyces starkeyi, Lipomyces kononenkoae, Lipomyces tetrasporus, Myxozyma melibiosi, Myxozyma mucilagina, Myxozyma kluyveri, Waltomyces lipofer, Zygozyma oligophaga and Zygozyma arxii. The detection of such aspirin sensitive arachidonic acid metabolites in representative strains of Lipomyces anomalus and the genus Dipodascopsis, emphasises the isolated position of these taxa in the genus Lipomyces and the family Lipomycetaceae, respectively. Finally using long chain fatty acid analyses, electrophoretic karyotyping and other phenotypic characters, a phylogenetic scheme is proposed for some genera in the Lipomycetaceae.

Isolation of a novel arachidonic acid metabolite 3-hydroxy-5,8,11,14-eicosatetraenoic acid (3-HETE) from the yeast Dipodascopsis uninucleata UOFs-Y128.

When arachidonic acid (AA) is added to the yeast Dipodascopsis uninucleata UOFS Y128, one of the major metabolites isolated and purified with the help of thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) is 3-hydroxy-5,8,11,14-eicosatetraenoic acid (3-HETE). The structure of this new AA metabolite was elucidated mainly by electron impact (EI) mass spectrometry (MS). Strikingly, the formation of this new metabolite was found to be inhibited by aspirin.

Attenuation of cutaneous reactivity to histamine by cetirizine and dexchlorpheniramine.

A double-blind cross-over study was performed in 12 healthy female volunteers comparing cetirizine di-HCl (10 mg) and sustained release dexchlorpheniramine maleate (6 mg) with respect to attentuation of histamine-induced skin wheals and subjective central nervous system (CNS) effects. Cetirizine was significantly more effective than dexchlorpheniramine in suppressing the size of wheals from 2 to 24 h after drug administration. In fact, at 24 h cetirizine was still as effective as 2 h after ingestion. Ten subjects receiving dexchlorpheniramine reported subjective symptoms relating to CNS depression, in contrast to only one subject given cetirizine.

Comparative bio-availability of theophylline whole and halved sustained-release tablets.

In a randomised, multiple-dose, cross-over study in 14 healthy volunteers, plasma theophylline concentrations were compared during a 12-hour dosing interval after repeated administration of theophylline (Euphyllin Retard; Byk Gulden) as whole and halved tablets. Bio-availability of theophylline from the halved tablets relative to the whole tablets was: 116% (100%, 134%) for the extent of absorption as judged by the area under the concentration time curve (AUC) and 115% (99%, 135%) for the rate of absorption as judged by maximum concentration (Cmax). The confidence levels for the 80-120% bio-equivalence range were 72% (AUC) and 76% (Cmax), those for the 80 and 125% range were 91% (AUC) and 91% (Cmax). The plateau times T75% Cmax, which characterise the sustained-released properties, were 8.5 +/- 2.9 hours (halved) and 8.3 +/- 2.5 hours (whole) during the 12-hour dosing interval. It is concluded that no clinically relevant deviations in steady-state plasma theophylline concentration and sustained-release properties are likely to result from breaking (halving) the film-coated tablets.

Pharmacokinetics of temazepam after day-time and night-time oral administration.

The pharmacokinetic disposition of temazepam was compared after a day-time and night-time dose in an open randomised crossover study. Twelve healthy male volunteers received a single oral dose of 20 mg temazepam in a soft gelatine capsule at 0900 h or 2200 h. Blood samples were taken immediately before dosing and at selected times over the 36-h period after each dose. The absorption of temazepam was slower after evening administration; the absorption half-life and time to reach maximal plasma concentration being 0.53 h and 1.67 h respectively, compared to 0.38 h and 1.02 h following morning administration. Considering distribution characteristics, evening administration produced a lower peak plasma temazepam concentration (362 ng/ml) compared with a day-time level of 510 ng/ml. Distribution half-life after night-time administration was increased compared with day-time administration (1.76 h vs 1.03 h). A significantly higher percentage of the drug, relative to Cmax, remained in the plasma at 8 and 24 h after evening dosing (39.3 and 15.4% compared to 24.7 and 11.2% following day-time administration). In spite of the half-lives of absorption, distribution and elimination all being longer after the evening dose, the overall bioavailability, as measured by the area under the curve (AUC) was comparable after the two times of administration. Similarly the difference in the mean residence time (MRT) of the two doses was within accepted limits. It is concluded that a chronopharmacokinetic effect was seen for temazepam; however it is unlikely to be of any clinical significance.

Ibuprofen bio-availability. A comparison of Brufen and Inza.

Ibuprofen in the form of Brufen 200 mg tablets and Inza 200 mg and 400 mg tablets was administered to 18 healthy adult volunteers (9 men and 9 women) in a single-dose (800 mg ibuprofen) open randomized cross-over bio-availability study. Tests revealed increased time required for 50% dissolution to take place for Inza tablets (40-47 minutes) relative to Brufen tablets (7 minutes). Maximum concentration and time to maximum concentration differed significantly (over 20%) between Inza and Brufen, being approximately 30% lower and 67% greater respectively in the case of Inza tablets. Area under plasma concentration time curves were comparable. These data suggest that the Inza tablets tested are not bioequivalent to Brufen 200 mg tablets. Clinical implications are discussed.