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Aim: To examine the effect of body position on clinically significant gastro-oesophageal reflux (GOR) in preterm infants., Methods: Eighteen preterm infants with clinically significant GOR were studied prospectively using 24 hour lower oesophageal pH monitoring. Infants were nursed in three positions (prone, left, and right lateral) for 8 hours in each position, with the order randomly assigned. Data were analysed using analysis of covariance., Results: The median (range) reflux index (RI) for the group was 13.8% (5.8-40. 4). There was no significant difference in the mean time spent in each position. RI (mean % (SEM)) was significantly less in prone (6. 3 (1.7)) and left lateral positions (11.0 (2.2)), when compared with the right lateral position (29.4 (3.2)); p<0.001. The mean (SEM) longest episodes (mins) of GOR were reduced by prone and left positions (8.6 (2.2) and 10.0 (2.4), respectively) compared with the right position (26.0 (3.9)); p<0.001. The mean (SE) number of episodes was reduced by prone (15.4 (2.8)) and left (24.6 (3.5)) positions when compared with right (41.6 (4.6)) (p<0.001)., Conclusions: Prone and left lateral positions significantly reduce the severity of GOR, by reducing the number of episodes and the duration of the longest episodes. Such positioning offers a useful adjunct to the treatment in hospital of preterm infants with gastro-oesophageal reflux.

Organotin compounds are ubiquitous in the environment. The general order of toxicity to microorganisms increases with the number and chain length of organic groups bonded to the tin atom. Tetraorganotins and inorganic tin have little toxicity. Because of their lipophilicity, organotins are regarded as membrane active. There is evidence that the site of action of organotins may be both at the cytoplasmic membrane and intracellular level. Consequently, it is not known whether cell surface adsorption or accumulation within the cell, or both is a prerequisite for toxicity. Biosorption studies on a fungus, cyanobacteria, and microalgae indicates that cell surface binding alone occurred in these organisms, while studies on the effects of TBT (tributyltin) on certain microbial enzymes indicated that in some bacteria TBT can interact with cytosolic enzymes. Microorganism-organotin interactions are influenced by environmental conditions. In aquatic systems, both pH and salinity can determine organotin speciation and therefore reactivity. These environmental factors may also alter selectivity for resistant microorganisms in polluted systems. Tin-resistant microorganisms have been identified, and resistance can be either plasmid or chromosomally mediated. In one TBT-resistant organism, an Altermonas sp., an efflux system was suggested as the resistance mechanism. Biotransformation of organotin compounds by debutylation or methylation has been observed. These reactions may influence the toxicity, mobility, and environmental fate of organotin compounds.

Two inorganic tin compounds, as well as mono- and tri-substituted methyl-, butyl-, and phenyltins were examined for their interactions with a hydrocarbon-using strain of Candida maltosa. Neither of the inorganic tins (SnII and SnIV) inhibited growth at concentrations up to 0.8 mM while binding to the yeast cells occurred to levels of 0.3 and 0.23 mM Sn/g cells, respectively. Neither inorganic tin caused leakage of potassium from the yeast cells. Among the organotins, tributyl- and triphenyltins caused total viability loss and near maximum potassium loss at initial concentrations of 0.08 mM. For these compounds binding to the cells increased with increasing initial concentrations to maximum values of 0.51 and 0.65 mM Sn/g cells respectively. The other organotin compounds were not inhibitory and did not cause potassium leakage from the cells. Tin from them became cell associated only in the cases of monobutyl- and monophenyl tin, which were bound at markedly lower levels (<0.1 mM Sn/g cells). These results are consistent with the conclusion that the inhibitory compounds can act on the yeast cell membrane but, although binding to the cells is a prerequisite for growth inhibition and cell leakage, no simple correlation was established between binding levels and toxicity effects.

This paper describes a collaborative audit between a large family planning and genitourinary medicine (GUM) service undertaken to ensure that all women presenting for termination of pregnancy (TOP) or IUD fitting were offered screening for chlamydia, were informed of a positive result, and were subsequently referred to GUM for full sexual health screening and contact tracing. Over a six month period in 1996 1072 patients were seen for either TOP (763) or W1) fitting (309) and of these 999 were offered a test which was performed in 988. Overall 38 positive tests were reported (3.8 per cent) but only two of 259 patients tested prior to lUD fitting were found to have chlamydia (<0.8 per cent). Only 27 of these 38 women (74 per cent) had information recorded in their notes that they had been given their result and 24 patients (63 per cent) were seen in GUM. The audit uncovered problems with documentation and cross-referencing of information which largely accounted for the failure to reach some of the standards set. An action plan has been formulated in an attempt to improve this aspect of the screening service. If more widespread screening for chlamydia is to be effectively implemented as recommended by the 31st RCOG Study Group on the Prevention of Pelvic Infection, then it is of importance that workable local protocols are in place including arrangements for partner notification and treatment. This will involve close collaboration between a range of specialities working in the sexual health field.

Inhibition of the growth of Saccharomyces cerevisiae was evident at concentrations of 0.5 mM Mn2+ or higher, but a tolerance to lower Mn2+ concentrations was observed. The inhibitory effects of 2.0 mM Mn2+ were eliminated by supplementing the medium with excess Mg2+ (10 mM), whereas addition of excess Ca2+ and K+ had negligible effect on Mn2+ toxicity. Growth inhibition by Mn2+, in the absence of a Mg2+ supplement, was attributed to Mn2+ accumulation to toxic intracellular levels. Mn levels in S. cerevisiae grown in Mg(2+)-supplemented medium were severalfold lower than those of cells growing in unsupplemented medium. Mn2+ toxicity was also influenced by intracellular Mg, as Mn2+ toxicity was found to be more closely correlated with the cellular Mg:Mn ratio than with cellular Mn levels alone. Cells with low intracellular levels of Mg were more susceptible to Mn2+ toxicity than cells with high cellular Mg, even when sequestered Mn2+ levels were similar. A critical Mg:Mn ratio of 2.0 was identified below which Mn2+ toxicity became acute. The results demonstrate the importance of intracellular and extracellular competitive interactions in determining the toxicity of Mn2+.

The magnesium content of Saccharomyces cerevisiae was found to vary by up to fivefold at differing stages of batch growth and during growth in the presence of differing magnesium concentrations. Excess Mg was primarily sequestered in vacuoles. Mn(2+)-uptake experiments revealed that Mg-enriched cells had a markedly reduced capacity for Mn2+ accumulation. For example, after 6 h incubation in the presence of 50 microM Mn2+, Mn levels were approximately twofold higher in cells previously grown in unsupplemented medium than in those from Mg-supplemented medium. These differences were further accentuated at higher Mn2+ concentrations and were not attributable to altered cell-surface charge or altered cell-surface Mn2+ binding. Cellular Mg status also influenced Mn toxicity towards S. cerevisiae. During exposure to 5 mM Mn2+, 50% reductions in the viability of cells with initial Mg contents of approximately 1400 and 2700 nmol (10(9) cells)-1 occurred after approximately 1.6 h and 3.6 h respectively. In cells containing 3300 nmol Mg (10(9) cells)-1, more than 75% viability was still maintained after 7 h incubation with 5 mM Mn2+. It is concluded that Mn2+ uptake and toxicity in S. cerevisiae are strongly influenced by intracellular Mg, possibly through Mg-dependent regulation of divalent-cation transport activity.

Fungal melanins are dark brown or black pigments located in cell walls. They also exist as extracellular polymers. Melanized fungi possess increased virulence and resistance to microbial attack as well as enhanced survival while under environmental stress. Melanins contain various functional groups which provide an array of multiple nonequivalent binding sites for metal ions. Pigmented Cladosporium cladosporoides was shown to biosorb 2.5- to four-fold more Ni, Cu, Zn, Cd, and Pb than albino Penicillium digitatum and at four- to six-fold higher rates. Metal desorption was significantly lower for extracellular melanin than from pigmented or albino biomass which indicated the strength of the melanin-metal bond. At equilibrium, tributyltin chloride (TBTC) concentrations of 2.5 mM, pigmented and albino Aureobasidium pullulans absorbed approximately 0.9 and 0.7 mumol TBTC mg -1 dry wt, respectively, whereas purified extracellular melanin exhibited uptake levels of approximately 22 mumol TBTC mg-1 dry wt at an equilibrium concentration of only 0.4 mM. Addition of melanin to the growth medium reduced the toxic effect of CuSO4 and TBTC due to melanin metal binding and sequestration.

This review addresses metal uptake specifically by yeast. Metal uptake may be passive, active or both, depending on the viability of the biomass, and is influenced by a number of environmental and experimental factors. Uptake is typically accompanied by a degree of ion exchange and, under certain conditions, may be enhanced by the addition of an energy source. Intracellularly accumulated metal is most readily associated with the cell wall and vacuole but may also be bound by other cellular organelles and biomolecules. The intrinsic biochemical, structural and genetic properties of the yeast cell along with environmental conditions are crucial for its survival when exposed to toxic metals. Conditions of pH, temperature and the presence of additional ions, amongst others, have varying effects on the metal uptake process. We conclude that yeasts have contributed significantly to our understanding of the metal uptake process and suggest directions for future work.

The applicability of the hard-and-soft principle of acids and bases in predicting metal adsorption characteristics in a biological context was investigated for metabolism-independent uptake of the metal ions Sr2+, Mn2+, Zn2+, Cu2+, Cd2+, and Tl+ by Saccharomyces cerevisiae. Metal adsorption increased with external metal concentration (5 to 50 microM), although some saturation of uptake of the harder ions examined, Sr2+, Mn2+, and Zn2+, was evident at the higher metal concentrations. Cation displacement experiments indicated that, with the exception of Tl+, relative covalent bonding (H+ displacement) of the metals was greater at low metal concentrations, while weaker electrostatic interactions (Mg2+ plus Ca2+ displacement) became increasingly important at higher concentrations. These results were correlated with curved Scatchard and reciprocal Langmuir plots of metal uptake data. Saturation of covalent binding sites was most marked for the hard metals, and consequently, although no relationship between metal hardness and ionic/covalent bonding ratios was evident at 10 microM metal, at 50 microM the ratio was generally higher for harder metals. Increasing inhibition of metal uptake at increasing external anion concentrations was partially attributed to the formation of metal-anion complexes. Inhibitory effects of the hard anion SO42(-) were most marked for uptake of the hard metals Sr2+ and Mn2+, whereas greater relative effects on adsorption of the softer cations Cu2+ and Cd2+ were correlated with complexation by the soft anion S2O32(-). Inhibition of uptake of the borderline metal Zn2+ by SO42(-) and that by S2O32(-) were approximately equal.(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory and brewing strains of Saccharomyces cerevisiae were compared for metabolism-independent and -dependent Sr2+ uptake. Cell surface adsorption of Sr2+ to live cells was greater in the brewing than in the laboratory strain examined. However, uptake levels were greater in denatured (dried and ground) S. cerevisiae, and the relative affinities of Sr2+ for the two strains were reversed. Results for the brewing S. cerevisiae strain were similar whether the organism was obtained fresh from brewery waste or after culturing under the same conditions as for the laboratory strain. Reciprocal Langmuir plots of uptake data for live biomass were not linear, whereas those for denatured biomass were. The more complex Sr2+ binding mechanism inferred for live S. cerevisiae was underlined by cation displacement experiments. Sr2+ adsorption to live cells resulted in release of Mg2+, Ca2+, and H+, suggesting a combination of ionic and covalent bonding of Sr2+. In contrast, Mg2+ was the predominant exchangeable cation on denatured biomass, indicating primarily electrostatic attraction of Sr2+. Incubation of live S. cerevisiae in the presence of glucose resulted in a stimulation of Sr2+ uptake. Cell fractionation revealed that this increased Sr2+ uptake was mostly due to sequestration of Sr2+ in the vacuole, although a small increase in cytoplasmic Sr2+ was also evident. No stimulation or inhibition of active H+ efflux resulted from metabolism-dependent Sr2+ accumulation. However, a decline in cytoplasmic, and particularly vacuolar, Mg2+, in comparison with that of cells incubated with Sr2+ in the absence of glucose, was apparent. This was most marked for the laboratory S. cerevisiae strain, which contained higher Mg2+ levels than the brewing strain.

Objective: To compare the clinical and mycological efficacy and patient acceptability of the oral antifungal itraconazole with vaginal clotrimazole in the treatment of vaginal candidosis., Design: A multicentre, single-blind, randomised, parallel group comparison of itraconazole and clotrimazole., Setting: 17 Genito Urinary Medicine clinics in UK hospitals., Subjects: Women with symptomatic, culture positive vaginal candidosis., Methods: Patients were randomly allocated 2 x 100 mg itraconazole capsules to be taken twice in a 24 hour period, or a 500 mg clotrimazole vaginal tablet. Clinical and mycological assessments were made at entry and after approximately seven and 35 days., Outcome Measures: Cure rate was defined in terms of mycological results, and patients were questioned on their opinion of treatment., Results: Of 214 patients, 109 received itraconazole and 105 clotrimazole with similar improvement in clinical signs and symptoms. Mycological cure rates one week after treatment were obtained in 72 of 97 patients (74%) in the itraconazole group and 64 of 89 patients (72%) in the clotrimazole group. Identical mycological cure rates six weeks after treatment were obtained with 40 of 79 patients (51%) receiving itraconazole and 39 of 78 patients (50%) receiving clotrimazole., Conclusion: Clotrimazole and itraconazole were found to be equally effective. A majority of patients receiving the latter preferred it to previous treatments.

Laser angioplasty systems with laser energy preferentially absorbed by atherosclerotic plaque may offer a safe method of plaque removal. This study evaluated the effect of blood upon selective energy absorption using a pulsed dye laser at 480 nm. Intra-arterial laser irradiation of normal rabbit femoral arteries demonstrated a perforation threshold energy with blood perfusion of 13.1 mJ per pulse compared to 87.9 mJ with saline (P less than .0001), indicating a deleterious effect in the presence of blood. An adverse effect upon arterial healing at 3 days was noted in sheep following intra-arterial irradiation during blood but not saline perfusion. Normal and atherosclerotic human aorta ablation thresholds differed significantly (P less than .0002) under saline (plaque: 20 mJ and normal: 120 mJ) but the difference under blood (plaque: 5 mJ and normal: 20 mJ) was not significant. We conclude that absorption of laser energy by blood can reduce the effect of differential absorption by endogenous chromophores in normal and pathologic vascular tissues and, therefore, removal of blood may be a prerequisite for selective ablation of atherosclerotic plaques.

The presence of anions in solution was found to inhibit the uptake of La3+, Cd2+, Pb2+, UO(2)(2+), and Ag+ by Rhizopus arrhizus biomass. The effects ranged from total inhibition of Cd2+ and Pb2+ uptake at equimolar concentrations of EDTA to no change in uptake of La3+ or UO(2)(2+)at 12-fold molar excesses of CI- or CO(3)(2-). No anion was found to enhance metal uptake levels, and the degree of inhibition generally followed the series: EDTA >or= >or= SO(4)(2)- C1- >or= PO(4)(3)- >or= glutamate >or= C0(3)(2)- The chemical equilibrium model REDEQLP was adapted to treat metal uptake by R. arrhizus biomass and used to predict the effects of anions in solution. Comparisons with the experimental results are made and discussed in light of the assumptions underlying the model.

Rhizopus arrhizus biomass was found to absorb a variety of different metal cations and anions but did not absorb alkali metal ions. The amount of uptake of the cations was directly related to ionic radii of La, Mn, Cu, Zn, Cd, Ba, Hg, Pb, UO(2), and Ag. The uptake of all the cations is consistent with absorption of the metals by sites in the biomass containing phosphate, carboxylate, and other functional groups. The uptake of the molybdate and vanadate anions was strongly pH dependent, and it is proposed that the uptake mechanism involves electrostatic attraction to positively charged functional groups.

In a prospective study, 100 women with recurrent vaginal candidosis were treated with miconazole, using two 100 mg vaginal pessaries a day for one week, then one pessary twice a week for three months followed by one pessary a week for a further three months. Fifty four women elected to continue using one pessary a week for longer than six months. Symptomatic vaginal candidosis did not occur in any patient during regular maintenance treatment. Of the 46 women who discontinued treatment before six months, however, 22 had a recurrence. Maintenance prophylactic treatment with miconazole pessaries appears to be an acceptable and effective method of preventing recurrent episodes of vaginal candidosis.

Out of 100 teenage girls attending a sexually transmitted disease clinic for the first time, 77 were found to be using a reliable method of contraception and had similar characteristics to teenage girls attending a family planning clinic. The 23 girls not using any reliable contraception exhibited a different pattern of sexual behaviour and were at high risk of unplanned pregnancy. Subsequently, another group of 23 girls not using contraception when seen at the sexually transmitted disease clinic were actively encouraged to attend a family planning clinic. Their risk of unplanned pregnancy was much reduced, although their pattern of sexual activity was unchanged. Ready availability of contraceptive advice for unprotected teenagers in sexually transmitted disease clinics would reduce their high risk of unplanned pregnancy.