The resource impact of wounds on health-care providers in Europe.

Most of the literature focuses on the resources required to manage particular wound types, rather than the cost of wounds to health-care organisations. Until this information is available, wound care is unlikely to be a management priority.

Impact of homozygosity for an amyloidogenic transthyretin mutation on phenotype and long term outcome.

Although amyloidogenic transthyretin (ATTR) mutations are common in several populations, such as black Americans, the small number of diagnosed patients homozygous for TTR amyloid and the short follow up in most studies has until now prevented an analysis of their phenotype. In Sweden, nine homozygous patients from eight families carrying the ATTR mutation Val30Met, which gives rise to fatal neuropathic amyloidosis (FAP), have been identified and have now been followed for up to 15 years. This has enabled an analysis of the phenotype of homozygous patients. Genetic testing and detection of amyloid deposits in the vitreous body or in intestinal or skin biopsies confirmed the diagnosis in all patients. The patients' symptoms were obtained from medical records. For comparison, we used a group of 35 heterozygous non-transplanted patients with FAP (18 men and 17 women), who had been evaluated at the Department of Medicine, Umeå University Hospital before their deaths. Vitreous amyloidosis was the most prevalent symptom in the homozygous group, and in two patients it was the only manifestation of the disease during their lifetime. The age at onset was not different from that of heterozygous patients, and their survival tended not to be shorter but actually longer than for heterozygotes. Homozygosity for the mutation associated with FAP, ATTR Val30Met, does not implicate a more severe phenotype for Swedish patients. The most common symptom was vitreous opacity, which may be the only manifestation of the disease. These findings point to the possibilities of different pathways for amyloid formation, or the presence of hitherto unknown genes operating in amyloid formation.

Low sex-hormone-binding globulin concentration as independent risk factor for development of NIDDM. 12-yr follow-up of population study of women in Gothenburg, Sweden.

Serum sex-hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were evaluated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM), myocardial infarction, stroke, and premature death in a prospective study of 1462 randomly selected women, aged 38-60 yr, over 12 yr of observation. In multivariate analysis, taking only age into consideration as a confounding factor, low initial concentration of SHBG was significantly correlated to the incidence of NIDDM and stroke, and high initial concentration of CBG was correlated to the incidence of NIDDM. There were also significant correlations between SHBG and CBG concentrations on one hand and possible risk factors for the end points studied, such as serum triglycerides, serum cholesterol, fasting blood glucose, body mass, body mass index, waist/hip ratio, smoking habits, and systolic blood pressure, on the other. When these possible confounders, in addition to age, were taken into consideration in multivariate analyses, only the inverse significant correlation between SHBG and NIDDM remained. The increased incidence of diabetes was confined to the lowest quintile of SHBG values, where it was 5-fold higher than in the remaining group. This incidence was further increased to 8- and 11-fold in the lowest 10 and 5% of the values, respectively. We conclude that SHBG is a uniquely strong independent risk factor for the development of NIDDM in women.

Numerical model for intraosseous infusion of the human calvarium for hydrocephalus shunting.

Hydrocephaly is the defective absorption of cerebrospinal fluid (CSF) into the blood stream. This work is an experimental and computational fluid dynamic modelling study to determine the permeability of the diploë as a potential receptor for CSF. Human calvariae were studied by micro-CT to measure their porosity, the area of flow and develop model geometry. Pressure-flow measurements were conducted on specimens to determine their permeability in the physiological and transverse flow directions to compare with numerical results. The overall porosity and permeability of the calvaria were spatially variable. Results suggest an order of magnitude increase in permeability for a 14% increase in overall porosity based on a small number of samples. Numerical results fell within the experimental infusion tests results. Due to the difficulty and ethical considerations in obtaining adolescent skull samples to perform large-scale testing, the developed model will be invaluable.

Transfer RNA modification: influence on translational frameshifting and metabolism.

Transfer RNA modification improves the rate of aa-tRNA selection at the A-site and the fitness in the P-site and thereby prevents frameshifting according to a new model how frameshifting occurs [Qian et al. (1998) Mol. Cell 1, 471-482]. Evidence that the presence of various modified nucleosides in tRNA also influences central metabolism, thiamine metabolism, and bacterial virulence is reviewed.

Dietary habits and incidence of noninsulin-dependent diabetes mellitus in a population study of women in Gothenburg, Sweden.

Dietary intake as initially estimated in a cross-sectional study has been related to the 12-y incidence of diabetes mellitus in a prospective study of 1462 women. In addition, all 50-y-old women (n = 352) were subjected to an intravenous glucose tolerance test. Because of the sampling procedure and a high participation rate the participants were representative of middle-aged women in the general population. No differences of statistical significance were observed concerning intake of energy and different nutrients. Neither did the number of meals nor the longest time between meals differ between women who developed diabetes and those who did not. Women with impaired glucose tolerance who developed diabetes did not differ from those who did not develop diabetes, concerning dietary intake. Body mass index was significantly higher in women who developed diabetes compared with other women. No specific dietary recommendations can be based on the results of this study.

Chromatographic properties of Sephacryl S-300 Superfine.

Sephacryl S-300 Superfine is a new gel filtration medium that consists of allyldextran crosslinked with N,N'-methylenebisacrylamide. It was shown to have a separation range for proteins that extends to 1--2 x 10(6) dalton. The gel filtration properties were characterized by fractionation of human serum and of bovine colostrum. Thyroglobulin from pig could be isolated in one step in a very pure form. The flow properties were characterized by the relationship between flow rate and pressure drop. It was shown that Sephacryl has very good flow properties in comparison with Sephadex G-200 and that it can be used in large-scale columns.

[Functionality of inhalation aerosols is inadequate or lost at low temperature]. / Inhalationsaerosolers funktion försämras eller uteblir i kyla.

Correct and safe performance of metered-dose inhalers are necessary for efficient treatment of asthma under all climatic conditions. The spray mechanism malfunctioned when canister temperature was below -15 degrees C. The range and propagation of the spray plume at canister temperatures below 10 degrees C deviated clearly from those at 20 degrees C. Also the composition and particle concentration of the spray plume at low temperatures differed from those at more normal temperatures. Information must be provided to the effect that a canister must not be cold when used.

Genetic parameters for feed intake, litter weight, body condition and rebreeding success in primiparous Norwegian Landrace sows.

The aim of this study was to estimate genetic parameters for feed intake recorded as farmers' perception of young sows' appetite for the first 3 weeks of lactation (APP) and feed intake recorded for one day in the 3rd week of lactation (FEED), litter weight (LW) at 3 weeks, sow body condition at weaning (BC) and the following five reproduction traits: weaning-to-service interval of 1 to 7 days (WSI7), weaning-to-service interval of 1 to 50 days (WSI50), delayed service or not (DELAYED), pregnant on first service or not (PREGNANT) and litter size in 2nd parity (NBT2). The analyses included data on 4606 Norwegian Landrace 1st-parity sows and their litters. The Gibbs sampling method was used. The traits DELAYED and PREGNANT were analysed as threshold traits and APP, FEED, LW, BC, WSI7, WSI50 and NBT2 were analysed as linear traits. The heritability estimates for APP and FEED were low (<0.1), whereas the estimates for DELAYED and PREGNANT were rather high (0.4 and 0.3). The heritability estimate for BC was 0.2. The genetic correlations confirmed the complexity of breeding for sow performance; selection for heavy 1st litters may lead to lower body condition at weaning, which in turn leads to lower reproductive performance and smaller litters in 2nd parity. Selection for higher sow feed intake would improve body condition, but the simple way of measuring feed intake tested in this study (APP and FEED) cannot be recommended because of the low heritability obtained for these traits.

Heritability of shoulder ulcers and genetic correlations with mean piglet weight and sow body condition.

The objective of this paper was to estimate the heritability for shoulder ulcers and the genetic correlations between shoulder ulcers, mean piglet weight and sow body condition. The analyses were based on information on 5549 Norwegian Landrace sows and their 7614 purebred litters. The genetic analysis was performed using the Gibbs sampling method. Shoulder ulcers were analyzed as a threshold trait. Sow body condition and mean piglet weight were analyzed as linear traits. The heritability of shoulder ulcers was estimated at 0.25 (s.d. = 0.03). The heritability for sow body condition was estimated at 0.14 (s.d. = 0.02) and that for mean piglet weight at 0.23 (s.d. = 0.02). The genetic correlation between shoulder ulcers and sow body condition was negative (-0.59, s.d. = 0.09). The genetic correlation between shoulder ulcers and mean piglet weight was positive (0.23, s.d. = 0.10) and the genetic correlation between sow body condition and mean piglet weight was negative (-0.24, s.d. = 0.10).

Genetics of growth in piglets and the association with homogeneity of body weight within litters.

The objective of this study was to examine the genetic basis of homogeneity in piglets and the genetic correlations with litter size and growth during lactation. Genetic parameters for variation in piglet BW within litters at birth and at 3 wk of age, and in the BW of individual piglets at 3 wk (BW3) were estimated from the Norwegian Landrace nucleus population. Data on BW3 were collected from 146,572 piglets from 14,045 litters in 58 herds. Body weight at birth and at 3 wk of age was recorded for 13,318 piglets from 5 nucleus herds. Litter data were evaluated using multivariate trait models. The heritability estimates for the SD of BW at birth and at 3 wk (SDBW3) were in agreement with the literature (0.10 and 0.08, respectively). The genetic correlation for the number of piglets born alive and the mean BW at 3 wk was negative (-0.40 +/- 0.07), and the correlation of number of piglets born alive with SDBW3 was close to zero (-0.03 +/- 0.11). The genetic correlation between the SD of BW at birth and SDBW3 was moderate (0.51 +/- 0.31). The mean BW at birth was genetically correlated with mean BW at 3 wk (0.59 +/- 0.16) but was independent of SDBW3 (0.08 +/- 0.27). The estimates of direct and maternal heritability for BW3 were 0.03 and 0.07, respectively, and the genetic correlation between the 2 components was negative (-0.43 +/- 0.10). The genetic correlation of SDBW3 with the maternal effect on BW3 was positive and strong (0.66 +/- 0.08), whereas a negative correlation was found with the direct effect on BW3 (-0.18 +/- 0.14). These results suggest that it is possible to select for mean BW at birth without an increase in within-litter heterogeneity at 3 wk of age. A more efficient strategy would be to consider both the direct and the maternal effects on BW3 in the genetic evaluation, together with SDBW3. Thus, it is possible to avoid the increase in within-litter heterogeneity that would occur as a result of selection performed at 3 wk on a litter trait such as mean BW.

Diabetes in hypertensive women: an effect of antihypertensive drugs or the hypertensive state per se?

A total of 226 women participating in a longitudinal study who were found to be hypertensive (initial values greater than or equal to 160 mmHg for the systolic blood pressure and/or greater than 95 mmHg for the diastolic blood pressure) were followed up with respect to the risk of developing diabetes during a 12-year study period. For each year of follow-up, information on whether each participant was taking antihypertensive drugs or not was collected. As a result there were 1339 'treatment years' and 1449 'non-treatment years' of follow-up. All 16 women who developed diabetes during the follow-up period were taking antihypertensive drugs at the time of onset of their diabetes. A similar observation was made when 145 women within the upper age-specific decentiles of systolic blood pressure were followed up in the same way. These results suggest that in hypertensive subjects antihypertensive drugs rather than the hypertensive state per se predispose to diabetes mellitus.

Antihypertensive drugs and glucose metabolism: comparison between a diuretic, a beta-blocker and felodipine, a new calcium antagonist in subjects with arterial hypertension and diabetes.

Felodipine, a new antihypertensive calcium antagonist, was compared with metoprolol, a beta-blocker, and hydrochlorothiazide, a diuretic, with respect to glucose tolerance in a randomized double-blind cross-over study consisting of 11 patients, of age range 50-70 years, who had developed diabetes during antihypertensive treatment. Each treatment period lasted for 10 weeks. The blood pressure was similar irrespective of treatment. Serum glucose levels during the oral glucose tolerance test were significantly lower when the patients were treated with felodipine than when they were taking hydrochlorothiazide. Serum insulin levels appeared to decrease at an earlier stage of the test when the patients were treated with felodipine, the calcium antagonist, than with the other two antihypertensive substances, which suggests that glucose tolerance is impaired to a lesser extent during treatment with the calcium antagonist. Glucose tolerance was never completely normalized with any of the drugs tested.

The separation of ribonucleic acids from Escherichia coli on lysin-agarose.

Lysine-agarose provides a simple means of separating RNA species of different moleecular weight. When RNA from Escherichia coli is added to a small column of lysine-agarose and elution is carried out at neutral pH with a shallow linear gradient of NaCl the RNA species are eluted according to size; 4S and 5S RNA species are completely separated and after a delay the 16S and 23S species are eluted as separate peaks. The process is very reproducible and the different species are eluted at a fixed salt concentration even when changes are made in the gradient, provided other conditions, under which the column is run remain constant.

Adiposity and adipose tissue distribution in relation to incidence of diabetes in women: results from a prospective population study in Gothenburg, Sweden.

The results refer to a 12-year longitudinal population study of women in Gothenburg, Sweden. Correlations were studied between initial adipose tissue amount and adipose tissue distribution on the one hand and incidence of diabetes and change in serum blood glucose concentration on the other. Body mass index, sum of two skinfolds and waist-to-hip circumference ratio were significantly associated with incidence of diabetes. The waist-to-hip ratio was also positively associated with an increase of serum glucose concentration in the fasting state during the followup period. The significant correlations remained in multivariate analysis and were independent of age, initial smoking habits, systolic blood pressure, intake of antihypertensive drugs and serum cholesterol, triglyceride and glucose concentrations. The correlations between the separate anthropometric variables and incidence of diabetes remained when the other anthropometric variables were considered as background factors. The distribution of fat to the abdominal region as well as the total amount of fat per se seem to be important risk factors for diabetes and the effect of one of these factors seems to add to the other.

Fasting serum insulin concentration and early insulin response as risk determinants for developing diabetes.

Among a cohort of 348 women aged 50 on entering a 12-year prospective study, the incidence of diabetes was increased (17.1%) during follow-up in those who initially had fasting glucose concentration above the upper quintile, a fasting serum insulin concentration above the upper quintile (14.9%), a disappearance rate of glucose below the lowest quintile in an IV glucose tolerance test (12.7%), or early insulin response below the lowest quintile (17.1%). The incidence in all women was 4.9%. By multivariate analysis, the highest risk was for high fasting serum insulin concentration. Obesity and treatment with antihypertensive drugs further increased the risk. An initial low early insulin response was not however a prerequisite for the development of manifest diabetes. Determination of fasting insulin concentration, especially in overweight hypertensive subjects, is of value in order to find out which subjects are at high risk of developing diabetes.

Effects of smoking cessation on insulin and cardiovascular risk factors--a controlled study of 4 months' duration.

OBJECTIVES: To investigate the effects on serum lipids, plasma fibrinogen, plasma insulin, plasma C-peptide and blood glucose, of smoking cessation after 4 months. To develop a group-based smoking intervention programme in primary health care. SETTING: Twenty health centres in primary health care in southern Sweden. SUBJECTS: Four hundred habitual smokers (> 10 cigarettes per day-1, > 10 years), recruited by advertisement in local papers. INTERVENTION: The smokers were randomized, after stratification for age and sex, to one intervention group (n = 200) and one control group (n = 200). The intervention group was offered supportive group sessions and free nicotine supplementation (patches, chewing gum). MAIN OUTCOME MEASURES: All participants were investigated at the start and after 4 months (medical history, physical examination, laboratory evaluation). Blood samples were drawn for determination of glucose, insulin and C-peptide, both in the fasting state and during an oral glucose tolerance test (OGTT), and for measurement of lipoproteins, fibrinogen, nicotine and cotinine. RESULTS: In the intervention group 98 of the subjects (48%) had quit smoking after 4 months. They were compared with the 156 subjects in the control group (91%) who were still daily smokers during the whole period. There were no significant differences in any variable between the two (total) experimental groups at baseline. Plasma nicotine and cotinine decreased (P < 0.001) in the intervention group following smoking cessation, and weight increased by 2.7 kg. In the intervention group HDL-cholesterol increased by 11% (P < 0.001), whereas HbA1c increased by 2% (P < 0.05) only in the control group. No changes occurred in levels of glucose, insulin, C-peptide and fibrinogen. CONCLUSION: The smoking cessation programme had a success rate of almost 50% over 4 months. Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance. A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism.

Discordant penetrance of the trait for familial amyloidotic polyneuropathy in two pairs of monozygotic twins.

BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is caused by mutated transthyretin in which valine at position 30 is substituted by methionine (ATTR Val30Met). FAP is inherited as an autosomal dominant trait with variable penetrance. CASES: Two pairs of DNA confirmed monozygotic twin brothers, 63 and 37 years of age respectively, who are heterozygous for the ATTR Val30Met gene, have been identified in Sweden. In the first twin pair (A), the onset of typical FAP symptoms occurred at the age of 48 for twin A1, whilst his twin brother (A2) is still free from FAP symptoms 13 years later. In the second pair of twins (B), the onset of polyneuropathy occurred at the age of 34 for the proband (B1), whilst his brother (B2) is healthy 3 years after the onset of his brother's disease. DISCUSSION: In the following, a detailed description of the clinical presentation of the Swedish twin pairs is provided together with a discussion of possible environmental factors initiating the onset of the disease.