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The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

Aim: To evaluate the diagnostic value of the skin-prick test and the atopy patch test in diagnosing basic food allergy in young children suffering from atopic eczema/dermatitis syndrome. Methods: 141 children, the majority under 2y of age (mean 16 mo) with atopic eczema/dermatitis syndrome were investigated using skin-prick and atopy patch tests for milk, egg, wheat and rye. Open diagnostic elimination challenge was done since this has been reported to be a reliable method in young children. Results: A positive challenge response was found to milk in 63 (45%), egg in 78 (55%), wheat in 61 (43%) and rye in 61 (43%). Sensitivity/specificity of the atopy patch test was 60%/97% for milk, 71%/97% for egg, 90%/94% for wheat and 93%/90% for rye. For the skin-prick test the corresponding figures were 41%/99%, 60%/97%, 13%/98% and 15%/99%. Conclusion: Patch testing was found to be a more sensitive method than the skin-prick test in diagnosing food allergy in children with atopic eczema/dermatitis syndrome, especially in those under 2 y of age. Many children with a negative skin-prick test result have a positive patch test result, especially in the case of cereals. A diagnosis of food allergy should be confirmed by elimination and in the research setting also by challenge.

Three laboratories present a harmonised system for the retrospective comparison of south west Asian heroin. It consists of an improved gas chromatographic (GC) profiling method and a computerised data retrieval. The investigations of the GC were necessary with a view to improve the reproducibility of the system. The necessity of a strict quality control is emphasized. The peaks of the GC profile were investigated for abundance, intensity, GC behaviour (reproducibility) and correlations; 16 of them were selected for describing the heroin profile in the database. The results from intra-lab profile comparisons are reported. The reproducibility of the analysis was good and the variation between the samples was large, thus, allowing conclusions with a high degree of certainty. The criteria of similarity were defined. The system is successfully running in all three labs. In connection with inter-laboratory comparison, the aspects of method harmonisation and standardisation are discussed. It appeared that the GC method is a very subtile one, urging for a strict standardisation between the three labs. Despite a long cooperation between three well-equipped and experienced labs, a more or less serious loss of reproducibility was noticed in the inter-lab results in comparison with the intra-lab results. The loss could for the greater part be attributed to the (limits of the) GC technique; a number of compounds, necessary for making the discrimination between samples, showed difficult chromatographic behaviour, leading to insufficient inter-lab reproducibility. Using the actual variables, improvements in performance can hardly be expected in the near future. The loss of reproducibilty implies that the number of false positive matches in a database search increases. This may strongly reduce the value of a relatively large, international database. The study shows that so far, the best option for international comparison is the analysis in a central laboratory. The idea of local determination at a large number of national labs and the use of a common database is not a realistic aim for this type of analysis.

Hospital admission rates for childhood asthma have increased in many countries. To study if this is also true for Norrköping Hospital, paediatric admission rates for asthma every fifth year were examined for the period 1973 to 1993. Admission rates were found to have fallen over the last 10 years, especially in children of school age. Among the younger age groups (below 5 years of age) a fall in admission rates was also observed over the last 5 years. This fall occurred in spite of reported increases in the prevalence of childhood asthma. The relative risk for admission due to asthma thus decreased from 1 in 1973 to 0.09 in 1993. The readmission rate has been stable. The mean length of stay in hospital for asthma decreased significantly. The observed decreasing trend in hospital admissions for childhood asthma is contrary to that found in many other countries. Possible explanations are discussed.

We report a prospective study of 232 consecutive patients with hip fractures. All were over 64 years of age and living independently before admission to a geriatric orthopaedic ward. We assessed the value, at admission, of predicting factors for independent living at one year after injury. The most important factors were: (1) preinjury function in activities of daily living (grade A or B on the Katz et al (1963) scale); (2) absence of other medical conditions which would impair rehabilitation; and (3) cognitive function better than 7 on the Pfeiffer (1975) mental questionnaire. The odds ratios (95% CI) for these three predictors were 3.5 (1.3 to 9.1), 2.9 (1.3 to 6.1) and 2.4 (1.9 to 4.9), respectively. When all predictors were positive at admission, 92% were living independently at one year; with one, two or three negative predictors, the percentages living independently were 76, 61 and 27, respectively. The median values of the total number of days in hospital, irrespective of diagnosis, during the first year were 12, 24, 29 and 149 days for the four groups. The mortality at one year was predictable on admission only by the number of medical conditions: with no other diagnosis than the fracture the mortality was 0%; with one or two additional conditions the mortality was 14%; and with three or more additional diagnoses it was 24%. These simple and robust predictors can be used to optimise resources for rehabilitation.

Computerized methods for classification of illicit Leuckart amphetamine are presented. The classifications are done on two hierarchical levels, aiming at batch relations and source relations, respectively. The results of the computerized classification versus those of the corresponding visual profile classification are discussed, as far as the second level is concerned. The results of five series of controlled syntheses are also presented.

In a prospective randomized study the effect of the use of an intraoperative indwelling urethral catheter (IUC) on urinary complications was investigated in patients undergoing spinal fusion. Two groups were formed; 16 patients received an intraoperative IUC and 16 patients had no intraoperative catheter (NC). All patients were, if necessary, intermittently catheterized in the postoperative period. Seven of the patients in the IUC group had positive cultures, defined asor = 100,000 CFU/ml, compared with two patients in the NC group (n.s.). Another four patients in the NC group had culturesor =10000 CFU/ml. Thirteen patients in the IUC group and 14 patients in the NC group had positive dip slides. The largest received urine volume in each patient at one intermittent catheterization did not differ significantly between the groups. However, in three patients in the NC group the volumes exceeded 1000 ml. Thus, irrespective of treatment dip slides showed bacteriuria in 84% of the patients. Perioperative indwelling catheters do not seem to cause many more infection complications than no bladder drainage during surgery, and the advantages of reduced risk of bladder distension injury and more accurate monitoring of fluid balance suggest their use.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

To evaluate the diagnostic value of the skin-prick test and the atopy patch test in diagnosing basic food allergy in young children suffering from atopic eczema/dermatitis syndrome.141 children, the majority under 2 y of age (mean 16 mo) with atopic eczema/dermatitis syndrome were investigated using skin-prick and atopy patch tests for milk, egg, wheat and rye. Open diagnostic elimination challenge was done since this has been reported to be a reliable method in young children.A positive challenge response was found to milk in 63 (45%), egg in 78 (55%), wheat in 61 (43%) and rye in 61 (43%). Sensitivity/specificity of the atopy patch test was 60%/97% for milk, 71%/97% for egg, 90%/94% for wheat and 93%/90% for rye. For the skin-prick test the corresponding figures were 41%/99%, 60%/97%, 13%/98% and 15%/99%.Patch testing was found to be a more sensitive method than the skin-prick test in diagnosing food allergy in children with atopic eczema/dermatitis syndrome, especially in those under 2 y of age. Many children with a negative skin-prick test result have a positive patch test result, especially in the case of cereals. A diagnosis of food allergy should be confirmed by elimination and in the research setting also by challenge.

Three laboratories present a harmonised system for the retrospective comparison of south west Asian heroin. It consists of an improved gas chromatographic (GC) profiling method and a computerised data retrieval. The investigations of the GC were necessary with a view to improve the reproducibility of the system. The necessity of a strict quality control is emphasized. The peaks of the GC profile were investigated for abundance, intensity, GC behaviour (reproducibility) and correlations; 16 of them were selected for describing the heroin profile in the database. The results from intra-lab profile comparisons are reported. The reproducibility of the analysis was good and the variation between the samples was large, thus, allowing conclusions with a high degree of certainty. The criteria of similarity were defined. The system is successfully running in all three labs. In connection with inter-laboratory comparison, the aspects of method harmonisation and standardisation are discussed. It appeared that the GC method is a very subtile one, urging for a strict standardisation between the three labs. Despite a long cooperation between three well-equipped and experienced labs, a more or less serious loss of reproducibility was noticed in the inter-lab results in comparison with the intra-lab results. The loss could for the greater part be attributed to the (limits of the) GC technique; a number of compounds, necessary for making the discrimination between samples, showed difficult chromatographic behaviour, leading to insufficient inter-lab reproducibility. Using the actual variables, improvements in performance can hardly be expected in the near future. The loss of reproducibilty implies that the number of false positive matches in a database search increases. This may strongly reduce the value of a relatively large, international database. The study shows that so far, the best option for international comparison is the analysis in a central laboratory. The idea of local determination at a large number of national labs and the use of a common database is not a realistic aim for this type of analysis.

A total of 17 patients with nummular psoriasis were treated with 0.1% betamethasone valerate stick on the right-hand-side of the body and with 0.1% betamethasone valerate ointment on the left twice a day for 4 weeks. The trial was performed open, and the patients were Bssessed at the beginning and at the end of the study. One patient dropped out because of lack of compliance. The study included an overall clinical and photographic assessment, assessment of the lesion area, scaling, colour and thickness, the amount of betamethasone valerate used during the trial, and a questionnaire on patients' opinions concerning the hygienic and cosmetic qualities of the stick. No significant difference was found in scaling and colour, but lesions studied were thinner when treated with the steroid stick. In most patients the overall clinical and photographic assessments showed that there was a better effect with the 0.1% betamethasone valerate stick than with 0.1% betamethosone valerate ointment. From a hygienic and cos...

We evaluated the efficacy of once-daily versus twice-daily treatment with budesonide, delivered by a Turbuhaler(R), in the management of children with stable asthma in a randomized, double-blind, parallel-group study involving 206 children (age 5-15 years). After a 2-week run-in period during which the children were maintained on their usual dose of budesonide (200 microg or 400 microg/day), patients were randomized to receive the same daily dose in either two daily administrations (morning and evening) or as a single dose in the morning over a period of 12 weeks. The primary efficacy variable was morning peak expiratory flow (PEF). The mean morning PEF during the run-in phase was 271 L/min in patients randomized to once-daily treatment and 264 L/min in those randomized to twice-daily treatment. The mean change from baseline to the last 2 weeks of the treatment period in the two groups was -0.3 L/min (95% confidence limits -6.6 to +6.0) and 2.5 L/min (-4.3 to +9.3). The estimated difference between the groups was -2.8 L/min, with 90% confidence limits of -10.4 + 4.5; these were close to the limits regarded as indicative of equivalence (-10 to +10), and hence the difference was not regarded as clinically relevant. Similarly, there were no significant differences between the groups in regard to secondary efficacy measures such as spirometric tests and symptom scores. Both treatments were well tolerated. We conclude that once-daily administration of budesonide by Turbuhaler(R) is as effective as twice-daily treatment in the management of stable asthma in children treated with inhaled steroids at doses of 200-400 microg/day.

We report a prospective study of 232 consecutive patients with hip fractures. All were over 64 years of age and living independently before admission to a geriatric orthopaedic ward. We assessed the value, at admission, of predicting factors for independent living at one year after injury. The most important factors were: (1) preinjury function in activities of daily living (grade A or B on the Katz et al (1963) scale); (2) absence of other medical conditions which would impair rehabilitation; and (3) cognitive function better than 7 on the Pfeiffer (1975) mental questionnaire. The odds ratios (95% CI) for these three predictors were 3.5 (1.3 to 9.1), 2.9 (1.3 to 6.1) and 2.4 (1.9 to 4.9), respectively. When all predictors were positive at admission, 92% were living independently at one year; with one, two or three negative predictors, the percentages living independently were 76, 61 and 27, respectively. The median values of the total number of days in hospital, irrespective of diagnosis, during the first year were 12, 24, 29 and 149 days for the four groups. The mortality at one year was predictable on admission only by the number of medical conditions: with no other diagnosis than the fracture the mortality was 0%; with one or two additional conditions the mortality was 14%; and with three or more additional diagnoses it was 24%. These simple and robust predictors can be used to optimise resources for rehabilitation.

Comparison of profiles is a well established way to find links between confiscated drugs. It is a laborious and time consuming task to manually compare large numbers of profiles to find common-batch links. To facilitate the comparison a computerized method has been developed. It is described and applied to a set of amphetamine impurity profiles. From each profile, areas of selected peaks are fed to the computer. By using quotients of corresponding peaks, the computer finds pairs of closely related profiles. With a sufficient numbers of peaks, the method is tolerant to variations in intensity between profiles, random peak area variations and a few strongly deviating peak areas. The program was written in Q-basic from Microsoft and may be run on any IBM-compatible personal computer. The method may also be used for analyzing data from other forensic objects, when the descriptors chosen are affected by errors like those described in the text.

It has been claimed that the increase in the strength of growing bone is due to increased mineral content. The strength of collagen is based on intermolecular covalent cross-links, and it has also been proposed that cross-link changes increase bone strength. Measurements of the content of calcium, collagen, and water, as well as cross-link analyses, were performed on the tibial cortex of growing dogs. Within the age range studied (8-44 weeks), no changes in calcium content expressed as a percentage of dry bone weight were seen. Collagen content expressed as weight of hydroxyproline per dry bone weight showed a minor reduction during growth. However, water content decreased considerably up to an age of about 25 weeks, which implies a concomitant increase in the amount of bone material. Of the two cross-link main groups, reducible and nonreducible, it is only possible chemically to analyze the reducible. During the final part of the period of growth and mechanical maturation of the bones, the number of reducible cross-links decreases. This indicates a concomitant increase in the more stable nonreducible forms. The possible mechanical relevance of the chemical changes found during growth is discussed.

Mifepristone (RU 486; Roussel-Uclaf, Paris, France) is an antiprogesterone used for termination of very early pregnancy. The ripening effect of Mifepristone on the human pregnant cervix was studied in 42 healthy women from 7 to 11 weeks gestation. The women were randomly allocated to oral treatment of either 100 mg Mifepristone or placebo for 24 and 12 hours before vacuum aspiration. An objective method has been designed to measure the force necessary to step-wise dilate the cervix from 4 to 11 mm. Significant ( p

A procedure that ensures exact reduction and internal fixation of Bennett's fracture is presented. In cases with a large tubercular fragment, the internal fixation is performed with a lag-screw technique. If the fragment is small, a Kirschner wire is used as an implant. A special set of instruments that keeps the reduced fragment in position and guides the implant during the internal fixation process is also described.

The strength of bone has often been measured in previously frozen samples and the freezing and thawing effect on the strength properties has been considered negligible. By means of a specially constructed torsion machine and a new method for rixing the test bone into the machine, previously frozen bones have been compared to fresh controls. The previously frozen samples were significantly weaker, with an average difference of -- 4.6 per cent.

Male genital blood flow and its regulation have not been fully clarified. In the present study we employed a radioactive microsphere technique to estimate the blood flow simultaneously in the major urogenital organs of male rats. The recorded genital flow rates varied among the rats. The relative blood perfusion rates of the testicles, seminal vesicles and kidneys did not differ from one animal to another. However, the blood flow in the prostate gland was not correlated to the perfusion of any of the other investigated urogenital organs.

The cortical atrophy induced by a rigid internal fixation plate on diaphyseal bone was studied on the femora of seven dogs. When the plate, which had been in position for 7 months without previous osteotomy, was removed, a pronounced reduction of the cortical bone was observed in the previously plated section of the diaphyseal bone. The atrophy took the form of loss of cortical bone mainly caused by endosteal resorption with enlargement of the medullary cavity. Neither periosteal resorption nor formation of woven bone under the site of the plate were observed. The process of adaption to the changed stress and strain conditions, caused by the mechanical joint, i.e., implants and bone, was studied by means of a histological technique, and was still in progress after a period of seven months.

Trace impurities in amphetamine sulphate were studied by a highly sensitive gas chromatographic method. The concentration of these impurities varied considerably between batches whereas the variations within the batches were usually very small. The method is used for the assignment of seizures of amphetamine sulphate to common sources, which in turn may permit chains of illicit distribution of this drug to be traced.

Adult rabbits were divided into three equal weight-matched groups. Drill holes 2.3 mm in width were drilled through the midshaft of the right femur across both cortices. A sham operation was performed on the left femur and served as a control. Group I was given indomethacin, 5 mg/kg twice daily. Group II was given ibuprofen, 7.5 mg/kg twice daily. Group III was given a placebo solution. Each group was treated for five or eight weeks. The serum levels of indomethacin and ibuprofen were recorded during treatment. After the rabbits were killed the legs were dissected from soft tissue and stored in a freezer. After thawing, the bones were examined for torsional strength. Neither the indomethacin nor the ibuprofen groups regained their torsional strength during the treatment periods, as compared with the controls. Anti-inflammatory drugs probably bring about their effects by acting on the prostaglandin synthesis. Although the effects produced by the drugs are significant, it is still uncertain whether the effects are great enough to influence one's decisions regarding their use.

Chemical signatures of phenmetrazine hydrochloride were studied by gas chromatography. The inter-batch variations of the signatures were found to be large whereas the intra-batch variations were usually small. The method is used for the tracing of seized phenmetrazine hydrochloride samples to common sources, which in turn may permit further tracing back to chains of illicit distribution of this drug. The applicability of the method to other narcotics is also discussed.

The effects of a hydrocolloid dressing (Comfeel Ulcus) on the physical environment of chronic leg ulcers in 58 consecutive out-patients were investigated. Patients were subdivided into two groups of which Group 1 included 31 (53.4%) and Group 2, 27 (46.6%) patients. Twenty-three (39.7%) patients healed within 7 weeks (study period) and 49 (84.5%) within 1 year (follow-up period). Aerobic and anaerobic bacterial cultures as well as mycotic cultures were performed from ulcer bases of both groups of patients. In Group 1 a 3 mm punch biopsy was taken from the ulcer margins for histopathological examination. In Group 2 serum levels of iron, zinc, copper and selenium were measured and in these latter patients a mean temperature difference of 2.8 degrees C between the ulcer base and the skin surrounding the ulcer was found. There was no difference in ulcer pH in patients belonging to Group 2, independent of bacterial or fungal contamination. Low serum iron was found in 74.1% and anaemia in 40.7% of the patients in Group 2. No differences in ulcer healing were seen in these patients compared with those without iron-deficiency or anaemia. No differences were seen in serum iron, zinc, copper or selenium levels between good and poor healers. There were 22.2% ulcer relapses in Group 1 within a year of the start of the study, with no relapses in those 15 patients of Group 2 who used specially designed compression stockings.

By means of a new method with high precision (error 3.1 per cent), the maximum torque capacity of an entire long bone from an experimental animal was measured under standardized conditions within 10 minutes after sacrifice of the animal.

Minor components of cannabis resin with longer retention times than that of cannabinol have been analyzed by use of a combined gas chromatograph-mass spectrometer-computer system. The presence of 30 such components has been detected. The data obtained indicate that some of the components are hydroxy derivatives of cannabinoids related to olivetol.

By using a newly constructed pin instead of Kirschner wires in the traction absorbing wire (TAW) technique, the clinically observed sliding of the Kirschner wires and resulting skin problems are avoided. The pins and the internal fixation technique are described. In order to demonstrate the simplicity and reliability of the technique a follow-up study 7 years after performed surgery is presented. The late results are given of a series comprising the authors' first 10 consecutive cases of closed transverse olecranon fractures treated by this new technique of internal fixation.

The unfavourable effect of the rigid internal fixation plate on the strength (measured as maximum torque capacity) of the diaphyseal bone, with due attention to the importance of the screw holes, has been studied on the femora of 7 dogs. When the plates that had been applied for 7 months without previous osteotomy were removed, a significantly reduced maximum torque capacity was observed, as also a significantly reduced maximum angle of torsion, and a significantly changed distribution of the amount of bone mineral.

A common opinion among physicians is that some symptoms from the prostate gland are stress-dependent. However, no experimental support for this view has been presented. In the present study blood perfusion of the major genital organs of male rats were measured after they had been subjected to experimental "short- and long-term" stress stimuli. The blood-flow measurements were made by means of a radioactive microsphere technique. The used experimental "short-term" stress reduced the prostatic blood flow by approximately 50 percent. A decreased blood flow and a concomitant atrophy, indicating that the reduction in blood flow has been in force over a prolonged period of time, were noticed in all examined genital organs of the rats subjected to prolonged stress stimuli. The decreases in blood flow and weight were most pronounced in the prostate gland.

Adult rabbits were divided into three equal weight-matched groups. Drill holes 2.3 mm in width were drilled through the midshaft of the right femur across both cortices. A sham operation was performed on the left femur and served as a control. Group I was given indomethacin, 5 mg/kg twice daily. Group II was given ibuprofen, 7.5 mg/kg twice daily. Group III was given a placebo solution. Each group was treated for five or eight weeks. The serum levels of indomethacin and ibuprofen were recorded during treatment. After the rabbits were killed the legs were dissected from soft tissue and stored in a freezer. After thawing, the bones were examined for torsional strength. Neither the indomethacin nor the ibuprofen groups regained their torsional strength during the treatment periods, as compared with the controls. Anti-inflammatory drugs probably bring about their effects by acting on the prostaglandin synthesis. Although the effects produced by the drugs are significant, it is still uncertain whether the effects are great enough to influence one's decisions regarding their use.