Pseudomonas aeruginosa diversity in distinct paediatric patient groups.

Pseudomonas aeruginosa is a pathogen that often infects patients who are either immunocompromised or have local defects in host defences. It is known that cystic fibrosis (CF) patients are sometimes infected with certain clonal isolates. It is not clear whether these clonal isolates also infect non-CF patients and whether clonality of isolates occurs in other patient groups. The aim of this study was to investigate P. aeruginosa diversity and the occurrence of clones within five distinct paediatric patient groups susceptible to P. aeruginosa infection. P. aeruginosa isolates were cultured from 157 patients (CF first infection (CF-1 group) (29); CF chronic infection (CF-chronic group) (27); urinary tract infection (34); chronic suppurative otitis media (43); and intensive-care hospitalization/immunodeficiency (24)). All 202 phenotypically different isolates were tested for antimicrobial resistance and further typed by pulsed-field gel electrophoresis. Simpson's diversity index was calculated for the five groups. CF-chronic patients carried the highest number of distinct P. aeruginosa phenotypes and genotypes per culture. Isolates from the CF-chronic group were significantly less diverse than those from the other groups. A group of clonal isolates was observed among patients from the CF-chronic and CF-1 groups. These or different clonal isolates were not encountered among the three other patient groups. No characteristic resistance pattern could be identified among isolates from the distinct patient groups and among the clonal isolates. In conclusion, isolates of the CF-chronic group were less diverse than those in the other patient groups with P. aeruginosa infection; clonal isolates were not encountered in non-CF patients. Transmission of clonal CF isolates to other patient groups was not observed.

Determination of benzodiazepines in human urine using solid-phase extraction and high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated for the determination of benzodiazepines, on the market in Norway, and/or their metabolites in human urine. The following compounds were included: 7-aminonitrazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, alprazolam, alpha-hydroxyalprazolam, oxazepam, 3-OH-diazepam, and n-desmethyldiazepam. The method includes hydrolysis of urine samples (0.5 mL) with beta-glucuronidase at 60 degrees C for 2 h before solid-phase extraction with a polymer-based mixed-mode column. The analytes were quantified in multiple reaction monitoring mode using two transitions. Deuterated analogues were used as internal standards for all analytes except 7-aminonitrazepam and alpha-hydroxyalprazolam, which were quantified using 7-aminoclonazepam-d(4) and alprazolam-d(5), respectively. The concentration range was 0.1-8.0 microM for 7-aminonitrazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, alprazolam, and alpha-hydroxyalprazolam and 0.5-40 microM for the other compounds. The average recovery for the different analytes ranged from 56% to 83%. The between-day precision of the method was in the range of 3-12%. The limits of quantification were found to be between 0.002 and 0.01 microM for the different compounds. Comparison with other analytical methods was performed for method validation, using approximately 500 samples provided by the routine laboratory at the Norwegian Institute of Public Health. The LC-MS-MS method has proven to be robust and specific for the determination of benzodiazepines in urine. It has been routinely used for approximately 1800 samples in the past 7 months.

Tinea pedis and onychomycosis in Danish soldiers before and after service in ex-Yugoslavia.

Seventy-three 1-year-experienced Danish soldiers were examined for tinea pedis as well as onychomycoses before and after a duty period of 6 months in ex-Yugoslavia. The incidence of fungal infections was 16.4% before and 32.3% after their duty period abroad. At first investigation Trichophyton rubrum and T. mentagrophytes were dominant but onychomycosis and tinea pedis were found as well. In contrast, Candida albicans was the predominant pathogen in the second investigation. We explain this by means of the more aggressive nature that yeasts can show when host-parasite relations are disturbed or compromised. Twelve soldiers with positive mycology were offered treatment and the final investigation showed a cure rate of 50%. This result is satisfactory in view of the difficult sanitary conditions.

Ranitidine does not affect psoriasis: a multicenter, double-blind, placebo-controlled study.

BACKGROUND: Data from open studies suggest that ranitidine has a beneficial effect on psoriasis and is well tolerated. OBJECTIVE: Our purpose was to determine the effectiveness of ranitidine in a 24-week, multicenter, double-blind, placebo-controlled, dose-comparing study of 201 patients with psoriasis. METHODS: Patients with moderate to severe psoriasis who had stopped systemic antipsoriatic therapy, including PUVA and UVB, for at least 10 weeks were included. After a washout period of 2 weeks, patients were randomly allocated to use either ranitidine, 150 mg twice a day; ranitidine, 300 mg twice a day; or placebo for up to 24 weeks. Assessment with the Psoriasis Area and Severity Index was performed at weeks 3, 6, 9, 12, 18, and 24 after randomization. Reduction of the Psoriasis Area and Severity Index score by 70% at the completion of the study was considered a treatment success. RESULTS: The success rates at week 24 in the 300 mg, 600 mg, and placebo groups were 11%, 5%, and 12%, respectively. No significant differences were observed between the three treatment groups at any stage of the study. CONCLUSION: This study provides strong evidence that ranitidine does not affect the skin disease in patients with psoriasis.

PCR for detection of Chlamydia trachomatis in endocervical, urethral, rectal, and pharyngeal swab samples obtained from patients attending an STD clinic.

OBJECTIVE: To investigate, by use of the Amplicor PCR in a routine setting, the recovery rate of Chlamydia trachomatis in ano-rectal and pharyngeal swab samples obtained from males and females attending an STD clinic in relation to sexual practices, symptoms, and signs. DESIGN: Data regarding sexual practices, and symptoms and signs related to the rectum and pharynx, were obtained from 196 females and 208 males, including 31 homosexuals and eight bisexuals. Swab samples were obtained from the urethra, rectum, and pharynx from all the patients. An additional endocervical swab sample was obtained from the females. METHODS: All samples were analysed by the Amplicor PCR (Roche). SETTING: Rudolph Bergh's Hospital, a clinic for sexually transmitted diseases situated in the centre of Copenhagen, Denmark. RESULTS: The overall prevalence of urogenital C trachomatis infection was 9.2% (37/404). The specificity of the Amplicor PCR was 100% for both ano-rectal and pharyngeal swab samples. In females three (13%) of the 23 infections were detected only by testing an ano-rectal or throat swab sample. In homosexual males two (67%) of three infections were detected only by the anorectal swab sample. Ano-rectal intercourse without use of condom was reported by 44% of females and by 52% of homosexual males. Fellatio without condom use was reported by 91% of females, and 80% of heterosexual males practised cunnilingus. Pharyngeal infection, however, occurred only in females, and the presence of pharyngeal symptoms or signs seemed predictive for pharyngeal C trachomatis infection, for which the time of incubation or colonisation exceeded 3 months. The presence of ano-rectal signs or symptoms was not predictive for an ano-rectal C trachomatis infection. CONCLUSION: The Amplicor PCR can be used on ano-rectal and pharyngeal swab samples. Ano-rectal swab samples should be obtained in females and homosexual males at high risk of being infected. Pharyngeal samples should be taken in females at high risk of being infected, especially when pharyngeal signs or symptoms are present.

Sodium lauryl sulphate penetration in an in vitro model using human skin.

Because of their ability to impair the skin barrier function, detergents constitute a major risk factor for the development of irritant contact dermatitis. Sodium lauryl sulphate (SLS) is a commonly used detergent for experimental studies within the area of irritant contact dermatitis. In the present study, penetration of S35-labelled SLS was studied in an in vitro model using human cadaver skin. The investigations showed that SLS is capable of permeating the skin barrier when applied under occlusion. SLS could be detected in the dermis and the amount of SLS found here was shown to depend on the dose of SLS applied on the skin. Penetration of SLS continued after removal of the SLS applied as a patch test on the skin surface. Considerable inter-individual variation in the penetration of SLS was demonstrated between different donors.

[Utilization of cardiovascular drugs in Denmark from 1978 to 1990]. / Forbruget af hjerte- og kredsløbsmedicin i Danmark fra 1978 til 1990.

In Denmark, the total sale of medicine increased from 3.1 billion Danish crowns in 1981 to 5.9 billion Danish crowns in 1990. This increase of 91% must be seen in relation to changes in the consumer price index which increased by 77% during the same period. The greatest increase was observed in the sale of antacids and preparations for the treatment of peptic ulceration (189%), drugs for asthma (225%) and antihypertensive drugs (409%). Subdivision of the group of antihypertensive agents reveals an explosive increase in the sale of calcium-blockers (in 1990: a total of 158 million Danish crowns) and angiotensin-converting-enzyme (ACE)-inhibitors (in 1990: 100 million Danish crowns). Both of these therapeutic principles had been introduced in the nineteen eighties. During the same period, slighter decreases were observed in the consumption of diuretics (194 million Danish crowns in 1990) and beta-blockers (204 million Danish crowns in 1990). This development in the sales figures documents an alteration in the patterns of prescription by practitioners. It must, however, be emphasized that the drugs mentioned here have several different therapeutic indications, some of which were first established during the above mentioned decade. No randomized investigations in the treatment of hypertension are available in which recent therapeutic principles with calcium-blockers and ACE-inhibitors were compared with the previously well tested therapeutic principles involved in diuretics and beta-blockers.

Effects of flumazenil on cerebral blood flow and oxygen consumption after midazolam anaesthesia for craniotomy.

Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were measured by a modification of the Kety-Schmidt technique using i.v. xenon-133 in 20 patients undergoing craniotomy for supratentorial cerebral tumours. Anaesthesia was induced and maintained with midazolam, fentanyl and nitrous oxide. Pancuronium was given for neuromuscular block. The lungs were ventilated to normocapnia. The first flow measurements were performed approximately 1 h after induction of anaesthesia. At the end of operation the patients were allocated to two groups. Ten patients were given flumazenil 0.01 mg kg-1 and 5 min later the second flow measurement was performed. In the other 10 patients the second flow measurement was performed before the administration of flumazenil. Plasma concentrations of midazolam were measured at the time of each measurement of CBF. There was no difference between the groups in plasma concentration of midazolam, CBF or CMRO2. Flumazenil had no effect on CBF and CMRO2.

The effects of midazolam on cerebral blood flow and oxygen consumption. Interaction with nitrous oxide in patients undergoing craniotomy for supratentorial cerebral tumours.

Cerebral blood flow and the cerebral metabolic rate of oxygen were measured in 30 patients during craniotomy for supratentorial cerebral tumours by a modification of the Kety-Schmidt technique using Xenon 133 intravenously. Anaesthesia was induced with midazolam 0.3 mg/kg, fentanyl and pancuronium, and maintained with midazolam as a continuous infusion, fentanyl, pancuronium and nitrous oxide in oxygen or oxygen in air. The concentration of midazolam in the blood of 10 patients was about 300 ng/litre during two measurements; the patients' lungs were ventilated with N2O in oxygen. The concentration of midazolam in the blood of another 10 patients was doubled to about 600 ng/litre during the second flow measurement; the patients' lungs were ventilated with N2O/O2. The concentration of midazolam in the blood of the third group of 10 patients was doubled to 600 ng/litre during the second flow measurement; the patients' lungs were ventilated with oxygen in air. No relationship was found between the dose of midazolam and cerebral blood flow or oxygen consumption. Nitrous oxide in combination with midazolam also had no effect on these variables.

Ranking of the antipsoriatic effect of various topical corticosteroids applied under a hydrocolloid dressing--skin-thickness, blood-flow and colour measurements compared to clinical assessments.

In 10 patients with chronic plaque type psoriasis one or two plaques affected equally with psoriasis were chosen for study. Five punched out rings of a hydrocolloid dressing were applied to the psoriasis plaque(s). In each circular test area 20 mg of one of the following creams was applied: base, 1% hydrocortisone (DAK), 0.1% triamcinolone acetonide (Kenalogue), 0.1% betamethasone-17-valerate cream (Betnovate), and 0.05% clobetasol proprionate cream (Dermovate). The areas were occluded with a thin film of transparent hydrocolloid dressing (Comfeel Transparent Dressing), for 1 week. Non-invasive measurements (ultrasound skin thickness, laser-Doppler flowmetry, colorimetry) were performed before and after treatment. Therapeutic response was evaluated blindly by clinical score. The measurements showed a decline in blood flow, a decrease in skin thickness, and normalization of colour approaching that of normal skin, the more potent the corticosteroid used. The clinical scores showed the same: the more potent a corticosteroid used, the closer to the score of normal skin. Data on variability and applications of the methods are presented. The study concludes that potent corticosteroids occluded with a hydrocolloid dressing can clear psoriasis in 1 week. Short-course corticosteroid therapy appears harmless and relevant for clinical dermatology.

Leukotriene B4 in atopic dermatitis: increased skin levels and altered sensitivity of peripheral blood T-cells.

Employing a radioimmunoassay, de-proteinated suction blister fluid from 12 patients with active atopic dermatitis appeared to contain higher levels of the pro-inflammatory and immunomodulatory mediator leukotriene B4 (LTB4) than suction blister fluid from 12 non-atopic individuals. Indirect support for the identity of the mediator was obtained by HPLC of pooled samples. Nylon wool enriched T cells from six patients with atopic dermatitis and six non-atopic people preincubated with LTB4 (10(-10) M - 10(-8) M) expressed no statistically significant suppression in co-culture with mitogen stimulated autologous mononuclear cells, and there was no difference between atopic and non-atopic T cells in this respect. In contrast, LTB4 induced a dose-dependent reduction in the percentage of phenotypic Leu 2a (suppressor) cells leading to an increased helper/suppressor ratio in five atopic patients that was not observed in five non-atopics. Elevated skin levels of LTB4 may initiate or amplify dermal inflammation, and abnormal T cell response to the mediator may account for the increased helper/suppressor ratio characteristic of patients with atopic dermatitis.

Cell surface glycosylation patterns in psoriasis.

Cell surface carbohydrates are excellent markers of cellular differentiation and maturation processes due to their great structural and antigenic diversity as well as their known biosynthetic precursor/product relationships. Using a panel of monoclonal antibodies with well-defined carbohydrate specificities we have studied the expression of biosynthetically related antigens in normal and psoriatic skin. Two "families" of carbohydrate structures were investigated. One series of structures based on N-acetyllactosamine chains (type 2 chain: N-acetyllactosamine and fucosylated derivates hereof of H, Lex, Ley and sialyl-Lex) and another based on the simple mucin type core structures (type 3 chain: Tn, T and sialylated derivates hereof as well as the fucosylated derivative, H). Previously we have found these carbohydrate structures define distinct cell layers in stratified squamous epithelia of mucosa of the cheek, esophagus and uterine cervix. In normal and uninvolved epidermis, N-acetyllactosamine and T carbohydrates were found in the spinous cell layer, whereas the fucosylated derivates, H structures, were found in the granular cell layers above. The fucosylated and sialylated derivate of N-acetyllactosamine, sialylated Lex, had the same distribution as N-acetyllactosamine and T structures. This sequential expression of carbohydrates is similar to our previous findings in mucosa. However, in contrast to mucosa, normal skin basal cells did not label. The glycosylation pattern in psoriatic epithelium was changed in two ways. 1) Some carbohydrates (types 2 and 3 chain H and T) were expressed at an earlier stage of cell maturation. 2) The biosynthetic precursors to T structures, Tn and sialyl-Tn, which are not expressed in normal skin, and are often considered cancer-associated antigens, appeared in psoriatic skin. The Tn-antigen was expressed on basal and lower spinous cells, whereas the sialyl-Tn was only found on basal cells above the dermal papillae. The findings in the present work support previous studies of changes in cell surface glycosylation in psoriatic epidermis and demonstrate the appearance of tumor-associated antigens in highly proliferative, but benign, stratified epithelium.

Irritant patch testing: penetration of sodium lauryl sulphate into human skin.

To clarify the sources of variation in irritant patch testing, variability in delivery of the test substance from the patch test system was studied. An in vitro model was used to study the penetration of sodium lauryl sulphate (SLS) from a patch test system into the skin. Different formulations of SLS applied to the skin for 24 h were studied (aqueous solution and gels), but irrespective of the vehicle used permeation of SLS into the recipient phase was poor. Results were compared to in vivo patch testing in 12 subjects. Approximately 70% of the applied SLS in aqueous solution was released from the patch test system. Release from gels was poorer. High concordance between the in vivo and the in vitro model was found. No correlation was found between the amount of SLS left in the filter disc and the strength of the clinical reaction in vivo.

Antipsoriatic effect of semi-occlusive treatment--O2-consumption, blood flow and temperature measurements compared to clinical parameters.

Ten patients with plaque-type psoriasis were treated by applying semi-permeable hydrocolloid dressings (Com-feel, Coloplast, Denmark) and the effect compared to untreated skin. The treatment effect was evaluated by: (a) O2-consumption as measured by a TCM-2 oxygen-monitor; (b) blood flow as measured by laser-Doppler flowmetry; (c) temperature measurements using thermocouples; (d) a clinical score. The treatment effect was evaluated after 1, 2 and 7 days and although there was a significant and sustained improvement in the clinical score following Day 7 (P less than 0.05), this was not associated with a significant change in any of the objective measurements during the study (P greater than 0.05). In the same patients the clinical effect of occlusion was evaluated after 21 days in another area. A pronounced effect was observed comparable to, equal to, or better than that of crude coal tar given as daily applications followed by bathing. There was no significant change in any of the parameters at the sites of untreated psoriasis.

[Transdermal scopolamine to prevent postoperative nausea and vomiting after uterine curettage and termination of pregnancy. A double-blind clinically controlled study with placebo]. / Transdermal skopolamin som profylakse mod postoperativ kvalme ved abrasio uteri og abortus provocatus. En dobbeltblind klinisk kontrolleret undersøgelse med placebo.

A randomized double-blind clinically controlled investigation with a placebo was undertaken to investigate the prophylactic effect of transdermal scopolamine on postoperative nausea and vomiting after dilatation and curettage and termination of pregnancy. No significant difference was found between the placebo and transdermal scopolamine. On the other hand, the patients in the scopolamine group had significantly more postoperative discomforts which were attributable to the anticholinergic effect of scopolamine. Transdermal scopolamine cannot be recommended for the prophylaxis of postoperative nausea and vomiting following uterine curettage and termination of pregnancy.

[Prescription of psychopharmaceuticals. A survey of drug treatment at 10 psychiatric hospitals]. / Forskrivning av psykofarmaka. En oversikt over medikamentell behandling i ti psykiatriske sykehus.

This study describes a survey of the drugs prescribed to long-term psychiatric patients and psychogeriatric patients in ten Norwegian psychiatric hospitals. Of 1,124 patients, 12% received no psychotropic drugs and 14% were given a combination of more than three psychotropic drugs. Of 872 patients given neuroleptics, 81% received antipsychotic medication with low-dose neuroleptics and 27% received depot-neuroleptics. Hypnotics and minor tranquillizers were commonly prescribed together with neuroleptics and antidepressants. Anti-parkinsonian drugs were prescribed for 37% of those receiving neuroleptics. Neuroleptics, minor tranquillizers and anti-parkinsonian drugs were commonly given three times a day. The prescription pattern differed between the hospitals. Guidelines are suggested for more rational use of psychotropic drugs.

Antipsoriatic effect of local corticosteroids--O2-consumption and blood flow measurements compared to clinical parameters.

Ten patients with chronic plaque-type psoriasis were treated topically with the group IV corticosteroid clobetasol propionate cream (Dermovate) with and without occlusion with a semipermeable hydrocolloid dressing (Comfeel Coloplast, Denmark). The effect of treatment was compared with untreated skin and evaluated in terms of (a) O2-consumption as measured by the TCM-2-oxygen monitor from Radiometer, Denmark, (b) blood flow as measured by a laser-Doppler flowmeter (Perimed, Sweden), (c) temperature measurements using thermo-couples and (d) a clinical score. While steroid + occlusion had a very pronounced effect measured by all parameters and apparent after 24 h, the steroid alone was only marginally effective after 7 days. No placebo effect was detectable in untreated skin with the laboratory methods used. It is suggested that the methods described can be used to evaluate other treatment schedules. Recently it has been shown that measurement of oxygen consumption by transcutaneous O2 electrodes might reflect disease activity in psoriatic plaques. Transcutaneous O2 decreases when a tourniquet is applied around the extremity investigated and the decrease per minute has been used as a measure of the metabolism of normal and psoriatic skin. In a later study it was shown that stripping of the skin prior to measuring was essential as a diffusion barrier was present in the horny layer. It has been previously shown that occlusion of an area to which corticosteroid has been applied increases absorption as estimated by the intensity of blanching. In the present study the effect of occlusion and non-occlusion of corticosteroid treated sites in psoriasis has been compared using clinical and laboratory parameters.

Perivascular axillary block VI: the distribution of gelatine solution injected into the axillary neurovascular sheath of cadavers.

Axillary perivascular injection of 50 ml blue-stained gelatine was made in 20 cadavers, and a total dissection of the axilla was performed. The distribution of injected gelatine and the contact between nerves and gelatine were examined on cross-sections of the neurovascular bundle. The spread of gelatine was characterized by: restriction of gelatine to the neurovascular bundle, an upper border of the gelatine which was constantly found to be proximal to the coracoid process, and bulging of the gelatine towards the medial part of the axillary space. Cross-sections of the neurovascular bundle showed the nerves and vessels to be located in the periphery of the gelatine and in close contact with the lateral wall of the axillary space. The median and the ulnar nerves were in all dissections found to be in direct contact with the gelatine, whereas the radial, the musculocutaneous, and the axillary nerves did not always have direct contact with the gelatine. Abduction of the arm to 90 degrees brings the stretched neurovascular bundle close to the lateral wall of the axilla and this compromises perivascular circumferential spread of the injected gelatine. On the basis of the present investigation, it is hypothesized that insufficient circumferential spread is the cause of incomplete axillary blockades, and the perivascular injection of local anaesthetic should consequently be made with the arm along the side of the body.