Referral of young people attending a sexual assault referral centre to mental health services.

Mental health issues following sexual assault in young people are common but early intervention may improve outcome. A retrospective case-note review of 58 female patients aged between 13 and 18 attending The Haven Whitechapel, a sexual assault referral centre, demonstrated past emotional problems in 72% of those seen, and current emotional problems in 95% of those being followed up. Fifteen percent were already involved with adolescent mental health services (AMHS). All patients requiring and not already receiving input were referred to AMHS or in-house. Of 23 patients referred to AMHS, eight (35%) were accepted and the patients attended, seven (30%) were accepted but did not attend, six (26%) were declined and the outcome of two referrals was unknown. The prevalence of emotional problems and inconsistent referral outcomes demonstrate a need for closer links with AMHS, clearer referral criteria and improved referral pathways.

MFAME, N-methyl-N-D-fructosyl amphotericin B methyl ester, a new amphotericin B derivative of low toxicity: relationship between self-association and effects on red blood cells.

In aqueous solutions N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME), a novel amphotericin B derivative with low animal toxicity, similar to its parent antibiotic, exists in three forms: monomeric, soluble and insoluble aggregates in equilibrium [1]. The aim of our work was to examine the influence of medium composition on the MFAME self-association and the relationship between MFAME self-association and its toxicity towards red blood cells. The toxicity of MFAME in aggregated state towards red blood cells was tested by measuring the induction of potassium leakage and extent of haemolysis. The proportions of antibiotic species present in various aqueous media were determined by analysis of the UV-Vis spectra as a function of the antibiotic concentration. Numeric decomposition of the spectra allowed identification of four spectral species present in MFAME solutions: monomeric and three aggregated forms. Our results indicate that these aggregates, named type I, type II and type III, are different in terms of spectral properties, as well as effectiveness towards red blood cells. Soluble aggregate types I and III are the active forms of MFAME towards erythrocytes. The medium composition seems to be the main factor determining which type of antibiotic aggregate prevails in solution.

N-Methyl-N-D-fructosyl amphotericin B methyl ester (MF-AME), a novel antifungal agent of low toxicity: monomer/micelle control over selective toxicity.

Rational chemical modification of amphotericin B (AMB) led to the synthesis of sterically hindered AMB derivatives. The selected optimal compound, N-methyl-N-D-fructosyl amphotericin B methyl ester (MF-AME) retains the broad spectrum of antifungal activity of the parent antibiotic, and exhibits a two orders of magnitude lower toxicity in vivo and in vitro against mammalian cells. Comparative studies of MF-AME and AMB comprising the determination of the spectroscopic properties of monomeric and self-associated forms of the antibiotics, the investigation of the influence of self-association on toxicity to human red blood cells, and of the antibiotic-sterol interaction were performed. On the basis of the results obtained it can be assumed that the improvement of the selective toxicity of MF-AME could in part be a consequence of the diminished concentration of water soluble oligomers in aqueous medium, and the better ability to differentiate between cholesterol and ergosterol.

Comparative studies on cell stimulatory, permeabilizing and toxic effects induced in sensitive and multidrug resistant fungal strains by amphotericin B (AMB) and N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME).

N-Methyl-N-D-fructosyl-amphotericin B methyl ester (MFAME) is a new derivative of amphotericin B, which is characterised by low toxicity to mammalian cells and good solubility in water of its salts. The antifungal activity and effects of MFAME towards Candida albicans and Saccharomyces cerevisiae multidrug resistant MDR(+) and sensitive MDR(-) strains was compared with those of parent compound. The results obtained indicate that MDR(+) S. cerevisiae was sensitive to MFAME as well as to AMB. MFAME exhibited the same effects on fungal cells studied as parent antibiotic. The two antibiotics, depending on the dose applied induced cell stimulation, K+ efflux, and/or had a toxic effect.

[Devic disease: a rare cause of retrobulbar optic neuritis: a case report]. / Choroba Devica--rzadka przyczyna pozagalkowego zapalenia nerwu wzrokowego--opis przypadku.

A case of 58-year-old woman with recurrent retrobulbar optic neuritis (ron) and transverse myelitis is presented. The patient was admitted to the opthalmology unit because of acute right retrobulbar optic neuritis. In 1997 she complained of left retrobulbar optic neuritis. One year later transverse myelitis of thoracic spine with spastic paraparesis occurred. MRI examination showed T2 hyperintensive focus in the thoracic spine (Th8-Th9, probably demyelinisation). Nowadays MRI examination of the optic nerves and brain showed demyelinisation focus in the right optic nerve. There was no pathological changes in the brain. The diagnosis of Devic disease was established. Treatment with intravenous methyloprednisolon was administered with slight improvement. The pathology and clinical course of Devic disease are discussed.

[Micronized fenofibrate, decreased triglyceride levels, total cholesterol and LDL fractions in serum]. / Fenofibrat mikronizowany zmniejsza stezenie triglicerydów, a takze cholesterolu calkowitego i frakcji LDL w osoczu.

Elevated serum level of triglycerides is a classic indication for fibrates. Micronized fenofibrate is hypolipemic drug with proven safety and efficacy in a view of triglycerides reduction, but according to few papers published so far on the subject is also effective in decreasing elevated total and LDL cholesterol. The aim of study was to confirm results obtained from these few previous studies. Forty seven persons with lipid disturbances (25 males and 22 females, age range 34-71 yrs. mean 48.0) entered the study. Thirty two patients had a history myocardial infarction and fifteen persons without clinical symptoms of heart diseases. All of them were treated with micronized fenofibrate 200 mg daily. Micronized fenofibrate decreased serum concentration of total cholesterol by 13.4% (p < 0.01), LDL cholesterol by 21.2% (p < 0.001) and triglycerides by 39.5% (p < 0.001) in whole group of patients. Most beneficial effects were obtained in persons with mixed hyperlipidemia: reduction of total cholesterol, triglycerides and LDL cholesterol serum levels was 22.4% (p < 0.01), 52.5% (p < 0.0001), 25.4% (p < 0.01), respectively. In individuals with hypercholesterolemia a reduction of total cholesterol by 11% (p < 0.05) and LDL cholesterol by 15.4% (p < 0.05) was observed. In the group with hypertriglyceridemia or mixed hyperlipidemia reduction of serum triglycerides concentration by 33.5% (p < 0.05) was achieved. No significant change in serum HDL cholesterol level in any group was observed. The treatment with micronized fenofibrate was well tolerated. Our study shows that this drug is safe and seems to be effective in some cases with increased serum total and LDL cholesterol level as well.

HIV and associated infections.

Infection with human immunodeficiency virus (HIV), which leads to the acquired human immunodeficiency syndrome (AIDS), presents with a number of opportunistic infections whose management remains a major concern. Understanding their pathogenesis and interactions with the HIV, and applying this knowledge to diagnostic and therapeutic procedures, were the main topics of the conference organised by the Royal College of Physicians, with support from Glaxo Wellcome. As the role of associated infections in HIV progression becomes clearer, prophylaxis becomes a possibility. Various antiviral therapies show promise of prolonging survival among patients and it seems almost certain that the future lies in multidrug therapy.

Identification of the structural elements of amphotericin B and other polyene macrolide antibiotics of the hepteane group influencing the ionic selectivity of the permeability pathways formed in the red cell membrane.

The selectivity of the transmembrane permeability induced by polyene antibiotics was studied in human erythrocytes and related to the hemolytic potency of the drugs. The selectivity induced was differently, dependent on the antibiotic structure in aromatic (vacidin A, gedamycin) and nonaromatic heptaenes (amphotericin B, candidin). Aromatic heptaenes were more effective than nonaromatic in inducing permeability to K+. For both groups of antibiotics, permeability to K+ was not affected by substitution at the carboxyl group but important differences in the induction of permeability to H+, OH- and Cl- were found. The strongly hemolytic aromatic heptaenes vacidin A and gedamycin exhibited much higher protonophoric activity than the nonaromatic ones: amphotericin B, and candidin. The protonophoric properties of aromatic heptaenes were related to the presence of a free carboxyl group in the antibiotic molecule. Indeed the esterification or amidation of the carboxyl group of vacidin A or gedamycin eliminated the ability of the antibiotic to increase H+ conductance and consequently diminished their hemolytic activity to an important extent. Both groups of antibiotics differed also in the efficiency of anion permeability induction. Only unsubstituted aromatic heptaenes, at high concentration, induced Cl-/OH- exchange and conductive flux of Cl- in a concentration-dependent manner. Substitution at the carboxyl group of vacidin A or gedamycin eliminated this property. Amphotericin B as well as its carboxyl-substituted derivatives formed a pathway characterized by low K+ over Cl- selectivity, whatever the concentration. The hemolytic activity, related to K+ permeability increased by heptaenes was dependent on simultaneous increase of the permeability to anions, and net KCl influx. Carboxyl-substituted derivatives of aromatic heptaenes presenting a remarkably high selectivity for K+, had consequently a very poor hemolytic activity.

[Lovastatin in the treatment of hypercholesterolemia]. / Lowastatyna w leczeniu hipercholesterolemii.

In 9 clinics 177 patients (68 men and 109 women) aged 23-69 years with primary hypercholesterolemia (TC above 6.5 mmol/L) were treated with lovastatin for 12 weeks. The treatment was started with 20 mg daily. The dose was doubled every 4 weeks, if the total serum cholesterol level did not fall below 5.2 mmol/L. For 4 weeks before treatment with lovastatin all patients received placebo. After the first 4 weeks of therapy the mean TC level decreased significantly (from 8.09 mmol/L to 6.54 mmol/L) by 18.5%. In comparison with the results after placebo (the starting value), after the 8 weeks of the therapy the TC level reduction reached 22.4% and after 12 weeks 23.5%. The mean LDL cholesterol decreased by 26.1%, 30.8% and 32.9% after 4.8 and 12 weeks of lovastatin treatment respectively. An increase in HDL cholesterol by 5.9%, 6.0% and 7.6% and decrease in triglyceride level by 10.7%, 14.9% and 14.0% respectively was also observed. In 6 patients on lovastatin treatment symptoms of acute pancreatitis in 1 case, a cataract in 1 case and aggravation of coronary insufficiency in 4 cases were noticed. These symptoms in the light of our knowledge of the mechanism of action of the drug used and of its side effects described in other trials, may be considered of independent on lovastatin. The treatment was discontinued in 5 cases (because of gastrointestinal intolerance in 2 patients, of aggravation of coronary insufficiency in 2 patients and of pain in the right hypochondrium in 1 patient who himself decided to stop the therapy).(ABSTRACT TRUNCATED AT 250 WORDS)