Vancomycin penetration into biofilm covering infected prostheses and effect on bacteria

To evaluate the adequacy of penetration of antibiotics into biofilm, a novel in vitro model for prosthesis-related infection was developed. Sterile stainless steel orthopedic nuts were incubated with slime-producing Staphylococcus epidermidis. Biofilm-covered nuts were exposed to varying concentrations of vancomycin; then biofilms were harvested. Vancomycin levels in biofilm, as measured by fluorescent polarization immunoassay, far exceeded the MIC and MBC of vancomycin for the organism. Bacterial growth in biofilm was inversely related to vancomycin concentration in biofilm, but even extremely high drug concentrations did not eradicate bacteria embedded in biofilm. The MICs and MBCs for bacteria recovered from biofilm did not differ from those for incubating organisms. Thus, failure of glycopeptide antibiotics to cure prosthesis-related infection is not due to poor penetration of drugs into biofilm but likely due to diminished antimicrobial effect on bacteria in the biofilm environment.     

Influence of propellant composition on drug delivery from a pressurized metered-dose inhaler

Hydrofluoroalkanes (HFAs) are used to replace chlorofluorocarbons (CFCs) as non-ozone-depleting propellants for pressurized metered-dose inhalers (pMDIs). HFA 134a and HFA 227 are used in combination to precisely manipulate the density and vapor pressure of pMDI formulations. The influence of propellant composition on the dose delivery characteristics of a suspension-based pMDI formulation was investigated. The results showed that as the density of the propellant blends approached the density of the suspended drug particles, the formulation became more physically stable and exhibited the most consistent dose delivery and greatest respirable fraction. The mass median aerodynamic diameter of the aerosolized particles contained in the emitted dose also was decreased by using propellant blends with higher vapor pressures. The performance of a suspension-based pMDI formulation was optimized by varying the propellant composition using HFA 134a and HFA 227.     

Significance of a false-positive trisomy 18 multiple-marker screening test

We report our results in 24 children with malignant primary bone tumours of the distal femur treated with a Stanmore extendible endoprosthesis (SEER). This consists of a femoral component that can be lengthened, a constrained knee and an uncemented sliding tibial component which crosses the proximal tibial physeal plate perpendicularly. The average age of the patients at diagnosis was ten years and the mean follow-up was 4.7 years (2.5 to 7.9). The mean growth of the affected tibia was 76% (18 to 136) and of the fibula 83% (15 to 750) of the growth of the unaffected limb. Measurement of growth arrest lines showed that the mean growth of the proximal tibial physis on the affected side was 69% (43 to 100) of that of the normal side. The great variability in the growth of the physis cannot yet be explained.     

Stability studies of amino acid substitutions at tyrosine 27 of the staphylococcal nuclease beta-barrel

In order to help determine the extent to which side chain interactions within the staphylococcal nuclease beta-barrel affect its global stability, a full set of point mutants was generated for residue 27. Intrinsic tryptophan fluorescence was monitored during solvent denaturation with guanidine hydrochloride (GuHCl) and was used to calculate DeltaGH2O unfolding and m values for each mutant. In the wild type protein, residue 27 is a tyrosine which is at the first position of a type I' beta-turn, and which participates in both hydrophobic interactions and side chain to side chain hydrogen bonding. The hydrophobicity of the mutant residue was found to be the dominant factor in determining global protein stability within this series of nuclease mutants.     

Blood trauma in plastic haemodialysis cannulae

To investigate the haemolysis in haemodialysis cannulae, an in-vitro set up is built, using a unipuncture dialysis system. This system is connected to a bag with fresh calf's blood, by the cannula under test, mounted in a large bloodline (5 mm diameter). The blood characteristics are kept constant by means of a bicarbonate dialysate in the dialyser. During a 6 h period, haematological parameters are regularly samples. Flow through the cannulae is recorded, which is about 500 mL/min. Four different cannulae are tested and compared to the results obtained without any cannula in the circuit. In all cases a linear increase in plasma free haemoglobin levels is found after 6 h. The cannulae can be ranked from 8F catheter over 13G, 14G to 16G cannula, the latter producing the highest degree of haemolysis. When using plastic cannulae at high blood flows, their haemolytic effect may not be neglected.     

Activating Smoothened mutations in sporadic basal-cell carcinoma

Basal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTCH in basal-cell nevus syndrome. We report here the identification of activating somatic missense mutations in the SMO gene itself in sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate with adenovirus E1A to transform rat embryonic fibroblast cells in culture. Furthermore, skin abnormalities similar to BCCs developed in transgenic murine skin overexpressing mutant SMO. These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.     

Computerized prompts for cancer screening in a community health center

One hundred eleven (58%) of 191 adolescent inpatients previously admitted to the emergency wards at the Child and Adolescent Psychiatric Clinics in the cities of Uppsala and G?teborg participated in a 2-4 year follow-up evaluation. The prevalence, incidence, and stability of depressive symptoms, suicidal ideation, and suicide attempts among the adolescents, and predictors of follow-up functioning were examined. Although a majority of the patients substantially reduced their depressive symptoms over the 2-4 year period, a smaller group (13%), mainly girls (94%), continued reporting high symptom levels at follow-up, and one out of five adolescents had moderate-severe levels of suicidal ideation. The accumulated frequency of suicide attempts among the patients shortly prior to hospitalization and during the follow-up was 59% including two patients who committed suicide. Significant predictors of depressive symptom severity at follow-up were depressive symptom scores and V-diagnoses at inpatient assessment. Previous suicide attempts before hospitalization, high levels of self-reported depressive symptoms and nonintact family status at inpatient assessment predicted suicide attempts during the follow-up period. The high prevalence of attempted and completed suicide in this clinical group underscores the importance of developing effective treatments for suicidal adolescents.     

Vigabatrin-induced lesions in the rat brain demonstrated by quantitative magnetic resonance imaging

Previous research has indicated that individual foods or beverages are ingested independently and do not produce adjustments to the intake of other constituents in the diet (de Castro, 1993; Wilson, 1991). In order to eliminate time of day as a potential contaminant, the present study investigated the accommodation of foods and beverages into the amount ingested at large evening meals only. Adults (n = 601) were paid to maintain detailed diaries of the timings, quantities and preparation techniques of everything they ingested for seven consecutive days. With the exceptions of soup, beef and chicken, 12 out of 15 types of drinks or foods were found to add to the total calories ingested in evening meals without displacing calories ingested in other forms, while ingestion of non-caloric diet sodas was not associated with differences in intake. The fat and protein, but not carbohydrate, contents of the items correlated with a measure of the satiating properties of the particular food or beverage, namely the correlation between the amount ingested of the particular type and the amounts of other nutrients ingested in the meal. The results confirm that intake at a meal is quite elastic and can be significantly influenced by the presence or absence of particular components of the meal and their constituents.