Multi-objective optimization for the economic production of d-psicose using simulated moving bed chromatography.

The biocatalytic production of rare carbohydrates from available sugar sources rapidly gains interest as a route to acquire industrial amounts of rare sugars for food and fine chemical applications. Here we present a multi-objective optimization procedure for a simulated moving bed (SMB) process for the production of the rare sugar d-psicose from enzymatically produced mixtures with its epimer d-fructose. First, model parameters were determined using the inverse method and experimentally validated on a 2-2-2-2 lab-scale SMB plant. The obtained experimental purities (PUs) were in excellent agreement with the simulated data derived from a transport-dispersive true-moving bed model demonstrating the feasibility of the proposed design. In the second part the performance of the separation was investigated in a multi-objective optimization study addressing the cost-contributing performance parameters productivity (PR) and desorbent requirement (DR) as a function of temperature. While rare sugar SMB operation under conditions of low desorbent consumption was found to be widely unaffected by temperature, SMB operation focusing on increased PR significantly benefited from high temperatures, with possible productivities increasing from 3.4kg(Lday)(-1) at 20°C to 5kg(Lday)(-1) at 70°C, indicating that decreased selectivity at higher temperatures could be fully compensated for by the higher mass transfer rates, as they translate into reduced switch times and hence higher PR. A DR/PR Pareto optimization suggested a similar but even more pronounced trend also under relaxed PU requirements, with the PR increasing from 4.3kg(Lday)(-1) to a maximum of 7.8kg(Lday)(-1) for SMB operation at 50°C when the PU of the non-product stream was reduced from 99.5% to 90%. Based on the in silico optimization results experimental SMB runs were performed yielding considerable PRs of 1.9 (30°C), 2.4 (50°C) and 2.6kg(Lday)(-1) (70°C) with rather low DR (27L per kg of rare sugar produced) on a lab-scale SMB installation.

Tagging fast neutrons from an (241)Am/(9)Be source.

Shielding, coincidence, and time-of-flight measurement techniques are employed to tag fast neutrons emitted from an (241)Am/(9)Be source resulting in a continuous polychromatic energy-tagged beam of neutrons with energies up to 7MeV. The measured energy structure of the beam agrees qualitatively with both previous measurements and theoretical calculations.

Spray bacteriotherapy decreases middle ear fluid in children with secretory otitis media.

OBJECTIVE: Secretory otitis media (SOM) is characterised by persistent fluid in the middle ear cavity, but the cause is unknown. We investigated the clinical, bacteriological and immunological effects of treatment with probiotic bacteria on SOM. DESIGN: In this double-blind pilot/preliminary study, 60 children with long-standing SOM (median 6 months) who were scheduled for insertion of tympanostomy tubes were randomised to nasal spray treatment with Streptococcus sanguinis, Lactobacillus rhamnosus or placebo for 10 days before surgery. Clinical evaluation was carried out after 10 days of treatment. Middle ear fluid (MEF) was collected during surgery for quantification of cytokines and detection of bacteria by culture and polymerase chain reaction (PCR). Nasopharyngeal swabs were obtained before treatment and at surgery. RESULTS: Complete or significant clinical recovery occurred in 7/19 patients treated with S sanguinis compared to 1/17 patients in the placebo group (p<0.05). In the L rhamnosus treatment group, 3/18 patients were cured or much better (p = 0.60 compared with placebo). Spray treatment did not alter the composition of the nasopharyngeal flora or the cytokine pattern observed in the nasopharynx or MEF, except for a higher level of IL-8 found in the nasopharynx of L rhamnosus treated children. CONCLUSIONS: This study shows that spray treatment with S sanguinis may be effective against SOM. The mechanism for the effect remains to be investigated.

Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial.

OBJECTIVE: To study the effect of recolonisation with alpha streptococci with the ability to inhibit the growth of otopathogens ("interfering" activity) on the recurrence of acute otitis media in susceptible children and the effect on the frequency of secretory otitis media. DESIGN: Double blind, randomised, placebo controlled study. SETTING: Ear, nose, and throat clinic with three doctors. PARTICIPANTS: 130 children prone to otitis media aged between 6 months and 6 years, 108 of whom were eligible and followed for 3 months. MAIN OUTCOME MEASURES: Recurrence of otitis media during follow up and a normal tympanic membrane at the last valid visit. INTERVENTIONS: Children with no recurrences during the last month received phenoxymethylpenicillin (n=22), and those with a recurrence within 1 month received amoxicillin clavulanic acid (n=86), both twice daily for 10 days. These were followed by a streptococcal or placebo solution sprayed into the nose for a further 10 days. At day 60 the same spray was started for another 10 days. RESULTS: At 3 months 22 children (42%) given the streptococcal spray were healthy and had a normal tympanic membrane compared with 12 (22%) of those given placebo. This difference was shown separately for recurrences of both acute otitis media and secretory otitis media. CONCLUSIONS: Selected bacteria with the ability to inhibit the growth of common otopathogens can be used to protect against recurrent acute otitis media and secretory otitis media in children.

Inhibition of OM pathogens by alpha-hemolytic streptococci from healthy children, children with SOM and children with rAOM.

The present study was undertaken to elucidate the inhibitory activity of the normal nasopharyngeal flora against the three most common otitis media (OM) pathogens in healthy children, children with secretory otitis media (SOM) and children with recurrent otitis media (rAOM). Isolates of alpha-hemolytic streptococci (AHS) and OM pathogens were recovered from the tubal orifice in each child. The samples were taken from 20 healthy children under general anesthesia, from 19 children with SOM and 20 children with rAOM. The method used to test the bacterial interference in vitro was a modified agar overlay method. The AHS sampled from the tubal orifice of the healthy children were able to inhibit 92% of the S. peumoniae isolates, 74% of the non-typable H. influenzae isolates and 89% of the M. catarrhalis isolates. The corresponding figures for children with SOM and children with rAOM were: 73% of the S. pneumoniae isolates, 58 and 54% of the non-typable H. influenzae isolates and 86 and 89% of the M. catarrhalis isolates. The AHS from children with SOM and children with rAOM were significantly less capable of inhibiting the S. peumoniae and the H. influenzae isolates (P<0.001). There was no significant difference between the three groups of children regarding inhibitory activity against M. catarrhalis. The results suggest that the inhibitory activity of the normal bacterial flora at the tubal orifice against pneumococci and H. influenzae may be reduced in children with SOM and rAOM.

Perianal streptococcal dermatitis. The possible protective role of alpha-streptococci against spread and recurrence of group A streptococcal throat infection.

OBJECTIVE: To follow the spread of beta-haemolytic streptococci group A (GAS) within a family and examine the protective activity of normally occurring alpha-streptococci against GAS tonsillitis. DESIGN: Follow up of recurrent GAS throat infection within a family. SETTING: Intra familial spread of GAS. PATIENTS: A family of four, the mother suffering from recurrent streptococcal tonsillitis and a son with perianal streptococcal dermatitis. RESULTS: The strain of the GAS found in the perianal region of the boy was identical with that found in the throat of his mother. She had recurrent streptococcal tonsillitis, while the boy remained healthy in the throat. She lacked interfering alpha-streptococci in the throat, while the boy had a massive growth of alpha-streptococci in his throat with capacity to inhibit the growth of the streptococcal isolate. MAIN OUTCOME MEASURES: Infection with GAS within a family correlated with the growth-inhibiting activity of the alpha-streptococci in vitro. CONCLUSIONS: The study demonstrated the spread of GAS from a patient with streptococcal dermatitis to the throat of another person within the family, and the hindrance of induction of infection in patients carrying interfering alpha-streptococci.

In vitro inhibition of S. pneumoniae, nontypable H. influenzae and M. catharralis by alpha-hemolytic streptococci from healthy children.

The present study aimed to investigate the inhibitory activity of the normal epipharyngeal flora against the three most common acute otitis media (AOM) pathogens in healthy children, and to study if the inhibitory activity differs between alpha-hemolytic streptococci (AHS) sampled from the tubal orifice and from those sampled from the adenoid. A total number of ten isolates of AHS were collected from the tubal orifice and the adenoid, respectively, in ten children undergoing adenoidectomy or tonsillectomy. None of the children had a history of otitis media, neither secretory otitis media (SOM) nor AOM. The method used to test the bacterial interference in vitro was a modified agar overlay method. The results showed that the AHS from nasopharynx were able to inhibit the majority of the S. pneumoniae, nontypable Haemophilus influenzae and Moraxella catharralis isolates tested. The AHS isolates from the tubal orifice inhibited growth of 93% of S. pneumoniae, 79% of H. influenzae and 84% of M. catharralis isolates. The corresponding figures among isolates from the adenoid were 76, 48 and 62%. This difference in the inhibitory capacity between the AHS isolates collected from the adenoid, compared with the AHS collected from the tubal orifice, is statistically significant (P<0.01) and implies that it is important to know the exact sampling locality before conclusions are made concerning the significance of bacterial interference in the upper airways.

Tolerance and efficacy of interfering alpha-streptococci in recurrence of streptococcal pharyngotonsillitis: a placebo-controlled study.

A total of 342 patients with clinical signs of tonsillitis and suspected group A beta-haemolytic streptococci (GAS) aetiology, verified with rapid test and GAS culture, were enrolled in a randomized, placebo-controlled, double-blind, multicentre study. They received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococcal or placebo spray treatment in the ratio of 2 : 1. Pharyngeal status, throat culture and adverse events were investigated up to 75 days after treatment. The frequency of bacteriologically verified clinical recurrence was 13% in the alpha-streptococcal group and 15% in the placebo group at the follow-up on day 22. The corresponding figures at the last valid visit after 45-75 days were 19% and 30%, respectively, a statistically significant difference (p = 0.037). Furthermore, at the last valid visit 5% of subjects in the alpha-streptococcal and 12% in the placebo group were healthy carriers, bacteriological treatment failures, of GAS (p = 0.029). Treatment with alpha-streptococci and placebo spray were equally well tolerated. Thus, re-colonization with alpha-streptococci seem to hinder late recurrences of GAS pharyngotonsillitis.

Saliva-resistant coating of tablets prevents oral release of penicillin: plasma but not saliva equivalence.

OBJECTIVE: To investigate saliva and plasma concentrations of penicillin after the intake of a conventional phenoxymethylpenicillin (PcV) tablet and a tablet with saliva-resistant coating (PcVsr), both containing 1 g penicillin. METHODS: The study had an open randomized crossover design and involved 24 healthy subjects. Saliva and blood were sampled intermittently for 6 h after tablet intake. RESULTS: Within the first 10 min after tablet intake penicillin was detected in saliva in ten subjects taking PcV and in none taking PcVsr (P < 0.001). These initial saliva concentrations were short-lasting, but in some subjects 50 to 100 times higher than those following the peak concentration in plasma, i.e. at 40 min or more after swallowing. From 40 min and onwards the saliva concentrations of penicillin were very similar for the two formulations. The elimination of high initial saliva concentrations may diminish ecological disturbances of the mouth flora as well as removing the unpleasant taste of penicillin. The plasma concentrations of penicillin were similar for the two formulations throughout the 6-h sampling period and the mean ratio of the area under the plasma concentration-time curve was 99% for PcVsr in relation to PcV, the 90% confidence interval being 86-115%. The corresponding values for the maximum plasma concentration were 108% and 93 127%. The time to maximum concentration was 45 min for PcVsr and 41 min for PcV. Thus, with regard to standard criteria which are based on systemic (plasma) concentrations, the formulations were bioequivalent despite the substantial difference in initial local (saliva) concentrations. CONCLUSION: Saliva-resistant coating of tablets can prevent oral release of penicillin without affecting the plasma concentrations. From a clinical point of view both local and systemic equivalence should be established before bioequivalence is assumed.

Recolonization with selected alpha-streptococci for prophylaxis of recurrent streptococcal pharyngotonsillitis--a randomized placebo-controlled multicentre study.

In a randomized, placebo-controlled, double-blind, multicentre study, 130 patients with recurrence of group A beta-hemolytic streptococci (GAS) and clinical signs of pharyngotonsillitis were enrolled. The patients received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococci-inhibitory to GAS-or placebo spray treatment. Patients taking antibiotic treatment for at least 9 days and using the spray for at least 5 days were included in the efficacy analysis. In addition, recurrence within the first 5 days of spray treatment was classified as 'early treatment failure'. The clinical recurrences (bacteriologically verified) in the alpha- (n = 51) and placebo-treated (n = 61) patient groups were 2% (n = 1) and 23% (n = 14) respectively, in patients given spray for at least 5 days (p = 0.004). The inclusion of 'early treatment failures' reduces this difference (p = 0.064). Both treatments were equally well tolerated. Thus, alpha-streptococci given as a spray and used for at least 5 days significantly prevented recurrence of GAS pharyngotonsillitis.

Tolerance development and arterial and venous tissue-/plasma levels of glyceryl trinitrate and glyceryl dinitrate in patients treated with nitroglycerin infusion.

Venous vessels (vena saphena magna) and arteries (left internal mammary artery) from patients treated with long-term ( > 24 h) intravenous infusions of nitroglycerin (CAS 55-63-0, glyceryl trinitrate, GTN) prior to coronary by-pass surgery were studied. Tissue concentrations of GTN and its dinitrate metabolites were determined as well as plasma-concentrations of GTN and glyceryl dinitrates (GDN's) on both the arterial and the venous side. The relaxant effect of GTN on the isolated vein preparations was studied and compared with those from two other groups of patients, one not exposed to GTN and the other exposed to a short-term infusion of GTN. Wide variations were found both in plasma and in tissue concentrations of GTN and GDN's on the venous and the arterial side. However, no extraction across the arterial-venous bed could be observed. Correlations were found between the dose given and the concentrations of drug and metabolites in both venous and arterial plasma as well as between 1,2-GDN in venous plasma and venous tissue, between 1,2-GDN in arterial plasma and arterial tissue and the same applied to 1,3-GDN on the arterial side. No correlations were found between the tissue concentrations of drug or metabolites and the relaxation induced by GTN in vitro. Venous vessels from patients treated with long-term infusions of GTN showed a pronounced decrease in relaxation as compared to vessels from patients not treated with nitroglycerin infusions and a slight decrease as compared to veins from patients treated with a shortterm infusion.

Enterococcal endophthalmitis following cataract extraction, treated with ampicillin intravitreally.

A case of Enterococcal endophthalmitis developed following an extracapsular cataract extraction. The infection was successfully treated with intravenous and intravitreal ampicillin, but a secondary glaucoma led to a later enucleation. We report a case of postoperative endophthalmitis with an unusual etiology, which did not respond to common treatment.

Chromosomal aberrations in a patient with severe psychopathology.

The case of a female patient showing aggressive, compulsive, destructive behaviour, ritualistic faecal smearing, and hyperactivity is presented. The behaviour is long standing, therapy-resistant, and its aetiology is unknown, although it is seemingly associated with chromosomal abnormalities secondary to abnormal plasma factors.

Digital chest radiography with a large image intensifier. Evaluation of diagnostic performance and patient exposure.

A digital system for chest radiography based on a large image intensifier was compared with a conventional film-screen system. The diagnostic performance was evaluated with special reference to the digital monitor images with a modified version of receiver operating characteristic (ROC) analysis--free response ROC (FROC) analysis--on a chest equivalent phantom. Measurements of spatial resolution and energy imparted were also performed. The detectability of low-contrast objects as well as spatial resolution was better for the full-size film-screen radiographs than for both the digital monitor images and the 100 mm photofluorograms. The image-intensifier system has a potential for considerable dose savings in relation to the conventional technique provided that fluoroscopy is excluded in the positioning of the patients.

Pigment mutations in the mouse which also affect lysosomal functions lead to suppressed natural killer cell activity.

The impact of five pigment mutations in the mouse on natural killer (NK) activity was examined in inbred strains congenic for the respective mutation. Whereas the nature of pigmentation disorder was similar in the five mutant strains (beige, pallid, reduced pigmentation, pale ear, and sepia), all mutations except sepia also led to a significant change in lysosomal enzyme activities in the kidney. A significant reduction in NK activity was observed in the four strains with lysosomal impact, whereas homozygous sepia mice displayed normal NK activity. The pigment mutations analysed are located on different chromosomes and fail to cross-interact negatively with each other in the heterozygous mice. This would indicate that pigment mutations with a parallel impact on lysosomal enzyme activities probably always result in a reduction in natural killer cell activity.

A gene affecting liver activities of three glycosidases in the house mouse.

A gene locus is described controlling liver activities in the house mouse of three glycosidases, i.e., beta-galactosidase, beta-glucuronidase, and N-acetyl-beta-hexosaminidase. An allele conferring low activity is present in the inbred strain LIS/A, and an allele for high activity is present in A/BrAf mice. The three enzyme activities are correlated with each other. The possible linkage between this gene and the Bgs locus on chromosome 9 is discussed.

Comparison of diflunisal and acetylsalicylic acid in patients with rheumatoid arthritis.

A double-blind comparison of the clinical efficacy and tolerance of varying doses of diflunisal (DFS) and acetylsalicylic acid (ASA) was carried out in 15 patients with rheumatoid arthritis who were given no other antirheumatic medication. An effort was made to select appropriate anamnestic, functional and sociofunctional tests and to optimize their validity by careful measurements performed by the same specialized physiotherapist and occupational therapist. In addition, the serum concentration of DFS and salicylic acid were monitored by high-pressure liquid chromatography. The therapeutic effects of DFS was at least as good as that of ASA. Moreover, DFS was better tolerated; all 7 patients on DFS could sustain the maximum dose (1g) of this drug, while that of ASA (4g) was tolerated by only one of 8 patients. All these experienced side effects, necessitating drug withdrawal in 3 cases, one being a serious hepatotoxic reaction. DFS treatment, on the other hand, was associated with only one minor side effect. The side effect difference was statistically significant (p less than 0.01). The analyses of drug concentrations in serum verified that all patients were exposed to DFS and ASA as planned, adding safety to the judgement of the therapeutic effects. The findings support the view that the novel salicylic acid derivative DFS may offer a therapeutic advantage in the treatment of rheumatoid arthritis; it seems to have at least the same therapeutic effect as ASA an may be better tolerated.