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Biomedical subjects

A Lindholm

Publications and source records attributed to A Lindholm.

At least 37 records · Page 2Linked to original sources

Injectable dextranomer-based implant: histopathology, volume changes and DNA-analysis.

OBJECTIVE: To study the tissue reaction in and around the implant, the changes in implant volume and the DNA profile of the invading cells when a new substance, dextranomers in sodium hyaluronan solution (DiHA), was injected into experimental animals. MATERIALS AND METHODS: Nine pigs were followed up from 2 weeks to 3.5 months and 34 rats were followed up from 3 weeks to 16 months after injection of DiHA into the bladder in pigs and into the subcutaneous tissue in rats. Histopathological analysis was performed in 16 pig and 63 rat implants. In 31 of the rat implants the DNA profile was analysed. Changes in implant volume over time were estimated in 51 rat implants during the period up to 12 months after implantation. RESULTS: Histologically, in the early phases the area within and around the implant was fairly rich in cells, predominantly fibroblasts, inflammatory cells and giant cells of the foreign body type. Later in the process an increase in extracellular matrix around the microspheres and ingrowth of blood vessels was seen. No tissue necrosis or significant eosinophilia was observed around the implants. DNA measurements by flow cytometry revealed no aneuploid cells. There was a decrease in implant volume by 23% over a period of 12 months. CONCLUSIONS: DiHA does not induce any major tissue changes in and around the implants. No DNA changes were observed during the study period of 16 months. DiHA seem to be a safe and suitable injectable substance with good tissue-augmenting properties.

Animals↗

Muscle characteristics and plasma lactate and ammonia response after racing in Standardbred trotters: relation to performance.

Blood samples from the jugular vein and muscle biopsies (gluteus medius) in 25 Standardbred trotters were obtained 5-10 min after racing. The biopsies were analysed for fibre type composition and enzymatic profile and blood samples for plasma lactate and ammonia concentrations. Muscle characteristics, plasma lactate and ammonia concentrations after racing were compared with each horse's individual performance index (IPI). The IPI is calculated annually from the individual horse's racing performance (% placing 1, 2 or 3, total annual earnings, average earning per start, and best racing record), respectively, converted to and expressed as a percentage deviation from the average record of the same sex and age group. The IPI values were 100-116. Plasma lactate concentrations were 15.0-42.7 mmol/l (mean 31.3 mmol/l) and ammonia concentrations 65-210 micromol/l (mean 141 micromol/l) after racing. Fibre type composition varied among horses (range 9-27% for Type I, 32-54% for Type IIA, and 27-46% for Type IIB). Fibre type composition, enzyme activities, plasma lactate and ammonia responses to racing were not correlated to IPI. Ten of the horses also performed a submaximal test on the track, consisting of 5 incremental 1000 m heats at approximate speeds of 9.1, 9.5, 10.0, 10.5, and 11.1 m/s. Immediately after each heat a blood sample was drawn from the jugular vein for plasma lactate analysis. Plasma lactate response to exercise differed between horses, but no correlation was seen with IPI. Muscle characteristics, plasma lactate and ammonia concentrations after racing and lactate response to a submaximal track test did not correlate with current race performance expressed as IPI in a group of horses with average or better performance capacity at the time of testing. Analysis of lactate and ammonia in blood after racing is not a valuable tool to predict an individual performance index.

Age Factors↗

Muscle adenine nucleotide degradation during submaximal treadmill exercise to fatigue.

The aim was to investigate metabolic response in muscle during submaximal treadmill exercise to fatigue, with a special emphasis on adenine nucleotide degradation products such as inosine monophosphate (IMP) in muscle and hypoxanthine, xanthine and uric acid in plasma. Five Standardbred trotters performed treadmill exercise on 2 occasions, once at 7 m/s and once at 10 m/s. Venous blood samples were taken at rest, during exercise and at the end of exercise. Muscle biopsies were taken before and after exercise and muscle temperature was measured before and after exercise. Running time differed among horses and was 48-58 min at 7 m/s and 10-15.5 min at 10 m/s. Both lactate and uric acid concentrations in plasma showed a gradual increase during exercise at both 7 and 10 m/s. At the end of exercise, values for uric acid were higher and values for lactate lower at 7 m/s compared with at 10 m/s. No marked changes were seen in plasma concentrations of hypoxanthine or xanthine with exercise. Muscle glycogen decreased after exercise at both 7 and 10 m/s with a marked depletion seen in some fibres. Muscle lactate concentrations increased after exercise at both 7 m/s and at 10 m/s. No significant changes were seen in adenosine triphosphate (ATP), ADP and AMP concentrations, whereas IMP concentrations increased after exercise at both 7 m/s and at 10 m/s. The results of this study indicate that AMP deamination occurs with submaximal exercise and that development of fatigue may be related to adenine nucleotide degradation in muscle.

Adenine Nucleotides↗

Effects of potassium intake on potassium, sodium and fluid balance in exercising horses.

The aim of this study was to investigate the adaptation to an increased potassium (K+) intake in horses and to study whether the regulation of the post exercise K+, sodium (Na+) and fluid balances were altered by an increased K+ intake. Four Standardbred horses were fed 2 levels (4.1 and 5.4 mmol/kg bwt/day) of K+ for 17 days in a crossover design. The effects on K+, Na+ and fluid balance were studied both at rest and in response to 29 km exercise. K+, Na+ and fluid intakes and outputs were balanced within 24 h after a new diet had been introduced. Adaptation consisted primarily of an increased urinary K+ excretion, later followed by an increase in faecal excretion. The increased urinary K+ excretion was associated with an increased mass of urine (1.2-1.4 kg/day) compensated for by an increased water intake. The sweat Na+ concentration was increased on the highest K+ intake (from 123 +/- 5 mmol/l to 138 +/- 3 mmol/l) and the urinary Na+ excretion was lower post exercise on this diet. There were no differences in the magnitude of post exercise hypokalaemia between the diets, and plasma K+ concentration was still reduced 24 h post exercise even when the horses were fed the higher K+ diet. Adaptation to an increased K+ intake was rapid in these horses and consisted mainly of an increased urinary excretion. The response to exercise was unaltered by the increased K+ intake, except for an increased Na+ concentration in sweat.

Aldosterone↗

Insulin aspart: a novel rapid-acting human insulin analogue.

In order to improve therapy and increase the quality of life for diabetic patients, it has been of significant interest to develop rapid-acting insulin preparations that mimic the physiological meal-time profile of insulin more closely than soluble human insulin. Insulin aspart (B28Asp human insulin) is a novel rapid-acting insulin analogue that fulfils this criterion. The B28Asp modification weakens the self-association of the insulin molecule and provides a more rapid absorption from the sc. injection site. The preclinical evaluation in vitro and in vivo demonstrates that apart from the more rapid absorption, insulin aspart is equivalent to human insulin. Thus, insulin aspart is equivalent to human insulin on key in vitro parameters such as insulin receptor affinity, insulin receptor dissociation rate, insulin receptor tyrosine kinase activation, IGF-I receptor binding affinity, metabolic and mitogenic potency. In accordance with the equivalent in vitro profiles, the toxico-pharmacological properties of insulin aspart and human insulin are also identical. The available data for insulin aspart and other rapid-acting insulin analogues supports that in vitro assays are sensitive and valuable in the preclinical evaluation of insulin analogues. Clinical studies demonstrate that insulin aspart has a pharmacokinetic and pharmacodynamic profile superior to that of soluble human insulin. In Type 1 diabetic patients on a basal-bolus injection regimen, insulin aspart given immediately before the meals provides an improved postprandial glycaemic control and an improved long-term metabolic control, as compared to soluble human insulin given 30 min before the meals, without increasing the risk of hypoglycaemia. Taken together, the data support the hope that insulin aspart will allow the diabetic patient to combine a more flexible lifestyle with better glycaemic control, without any increased safety risk.

Journal Article↗

Improved postprandial glycemic control with insulin aspart. A randomized double-blind cross-over trial in type 1 diabetes.

OBJECTIVE: Insulin aspart is a novel rapid-acting insulin analog. This study was performed to compare the postprandial serum glucose control after administration of insulin aspart with that of unmodified human insulin. RESEARCH DESIGN AND METHODS: The trial was a double-blind double-dummy injection three-way cross-over study in 22 subjects with type 1 diabetes. Insulin aspart was injected subcutaneously immediately before the meal, and human insulin was injected subcutaneously 30 min before the meal or immediately before the meal. RESULTS: The postprandial glucose control as assessed by the excursion of serum glucose was superior with insulin aspart as compared with that with human insulin injected immediately before or 30 min before a meal (891 +/- 521 vs. 1,311 +/- 512 vs. 1,106 +/- 571 mmol.l-1.min-1, P < 0.0001 and P < 0.02). This was accompanied by a significantly lower glucose maximum concentration [Cmax(SG)] for insulin aspart than for human insulin injected immediately before the meal (13.5 +/- 3.5 vs. 16.4 +/- 3.4 mmol/l, P < 0.001). Insulin aspart was, on average, absorbed twice as fast as human insulin, with median time to insulin aspart Cmax(ins) on the order of 40 min, and the maximum concentration was approximately twice as high for insulin aspart. The relative bioavailability of the insulins indicated a similar extent of absorption. Insulin aspart was well tolerated. CONCLUSIONS: This study demonstrates the ability of insulin aspart to improve postprandial glucose control when compared with human insulin.

Adult↗

GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors.

Sera from 62 hepatitis C virus (HCV)-infected Swedish blood donors were tested by a nested polymerase chain reaction using primers targeting the 5'-noncoding region of the GB virus-C/hepatitis G (GBV-C/HGV) genome and an enzyme-linked immunosorbent assay that detects antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). Fourteen (22%) and 21 (34%) of the 62 blood donors were found to be GBV-C/HGV RNA and anti-E2 positive, respectively. None of the blood donors was positive for both GBV-C/HGV RNA and anti-E2. Thus, 35 of 62 (56%) HCV-infected donors had been exposed to GBV-C/HGV infection. At sequencing of the 14 GBV-C/HGV isolates, 12 were identified as subtype 2a and 2 as subtype 2b. One of 7 (14%) donors with mild liver disease such as steatosis and nonspecific reactive hepatitis had been exposed to GBV-C/HGV vs. 34 of 55 (62%) with chronic hepatitis with or without cirrhosis (P = 0.04). All other differences in histology were small between HCV and dual HCV GBV-C/HGV-infected donors. In conclusion, more than half of HCV-infected Swedish blood donors in this study were positive for either GBV-C/HGV RNA or anti-E2. GBV-C/HGV viremia and seropositivity were mutually exclusive.

Adult↗

Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group.

OBJECTIVE: To compare glycemic control obtained with the new rapid-acting insulin analog insulin aspart with that obtained with unmodified human insulin using algorithm-driven dosage adjustment. RESEARCH DESIGN AND METHODS: This was a multicenter randomized double-blind crossover study of 90 male subjects with type 1 diabetes. Insulin aspart or soluble human insulin was administered before meals, and NPH insulin was administered at bedtime as basal therapy. Each 4-week study period ended with a 24-h inpatient serum insulin and plasma glucose profile. RESULTS: The 24-h plasma glucose control obtained with insulin aspart, as assessed by excursions of blood glucose outside a predefined normal range (4.0-7.0 mmo/l), was superior (22% reduction in excursion, P < 0.01). Fructosamine levels remained unchanged with insulin aspart, with daytime glycemic control superior but nighttime glycemic control inferior. Eight-point home blood glucose profiles confirmed that insulin aspart significantly improved postprandial blood glucose control after lunch and dinner (P < 0.05) without deterioration of preprandial blood glucose control. Hypoglycemic episodes requiring third-party intervention were significantly fewer with insulin aspart than with human insulin (20 vs. 44 events, P < 0.002). Insulin aspart was well tolerated. CONCLUSIONS: In comparison with human insulin, insulin aspart can improve postprandial glycemic control as assessed by a reduction in hyper- and hypoglycemic excursions in people with type 1 diabetes. For its full potential to be realized, it will need to provide better control of nighttime hyperglycemia.

Adult↗

Effects of differently composed feeds and physical stress on plasma gastrin concentration in horses.

Plasma gastrin concentrations were determined in 6 Standardbreds (4 geldings and 2 mares) after 3 different meals consisting of unlimited amounts of hay (8-9 kg per horse), a restricted amount of hay (0.6 kg/100 kg body-weight) and grain (0.2 kg/100 kg body-weight) in combination or of grain alone (0.2 kg/100 kg body-weight). In another series of experiments the possible role of gastrin as a stress hormone was investigated. Plasma gastrin and cortisol concentrations were determined during fasting and compared with concentrations during hay feeding. In addition, gastrin and cortisol concentrations were determined before, during and after 2 kinds of physical exercise on a treadmill. Meal stimulation significantly increased the plasma gastrin concentration, irrespective of the meal composition. An immediate and large increase in plasma gastrin concentration was found when voluminous meals were given, whereas a small meal evoked a later onset of gastrin release, suggesting that gastric distention plays an important role in inducing gastrin release during a meal. Meals consisting of grain seem to evoke a slower onset and then a more prolonged gastrin response than a hay meal, possibly due to different emptying rates of the stomach. Nervous excitation may play a minor role in the activation of gastrin release in horses. No experimental support was obtained for the idea that gastrin acts as a stress hormone in the horse.

Animal Feed↗

Comparison of standardbred trotters exercising on a treadmill and a race track with identical draught resistances.

The responses in heart rate, plasma lactate and rectal temperature of standardbred trotters to draught loaded interval exercise on a treadmill and a race track were studied. The horses were exercised with incrementally increasing trotting speeds for two-minute intervals with draught loads of 10, 20 and 30 kilopond (kp) in three different tests. Each trotting interval was followed by two-minute periods at a walk without a draught load. Measurements of heart rate and plasma lactate were made at the end of each interval and the rectal temperature was taken at the end of the exercise. The heart rate and plasma lactate levels were significantly lower on the treadmill than on the track in the tests with 10 kp, but no significant differences were found between the treadmill and track exercise tests with the heavier draught resistances. No differences were observed in rectal temperature between treadmill and track conditions. From these findings it was concluded that the workload was significantly greater on the race track compared to the treadmill when the draught resistance was low (10 kp). Although the workload increased on both the race track and the treadmill as draught resistance increased, at the heavier draught resistances track exercise was no longer more demanding than exercise on the treadmill.

Animals↗

Genetic markers in standardbred trotters susceptible to the rhabdomyolysis syndrome.

The equine rhabdomyolysis syndrome (RHA) is believed to be multifactorial in origin; and could be caused by an interaction between genetic and environmental factors. In order to analyse its genetic background an association study was undertaken. Two sample groups of Standardbreds (Stb) which had suffered from RHA were compared to the total population of Swedish Standardbred trotters using recorded polymorphic genetic markers. The results showed that gene frequencies for several markers in the RHA groups differed significantly from those estimated for the total population. A rhabdomyolysis risk group could be characterised using 4 or 5 genetic marker loci.

Alleles↗

Clostridium difficile associated with acute colitis in mature horses treated with antibiotics.

Clostridium (C.) difficile, or its cytoxin, was demonstrated in faecal samples from 10 of 25 (40%) mature horses investigated with acute colitis treated primarily with antibiotics for disorders other than diarrhoea. C. difficile was not found in faecal samples from 140 horses without signs of enteric disorders, from 21 nondiarrhoeic horses treated with antibiotics, nor from 22 horses with colitis untreated with antibiotics. Except for C. difficile neither Salmonella nor any other investigated intestinal pathogen was isolated in any of the diarrhoeic horses. The findings strongly support some earlier reports that C. difficile is associated with acute colitis in mature horses treated with antibiotics. Of the 10 horses, 4 proved positive for C. difficile both in culture and in the cytotoxin test, 4 in culture only and 2 only in the cytotoxin test. Eight of 10 horses positive for C. difficile were or had recently been hospitalised, indicating that C. difficile may be a nosocomial infection in horses. All horses positive for C. difficile were treated with beta-lactam antibiotics.

Acute Disease↗

The association of erythromycin ethylsuccinate with acute colitis in horses in Sweden.

In Sweden there are several reports of mares developing acute colitis while their foals were being treated orally for Rhodococcus equi pneumonia with the combination of erythromycin and rifampicin. In this study 6 adult horses were given low oral dosages of these antibiotics, singly or in combination. Within 3 days post administration of erythromycin, in one case in combination with rifampicin, 2 horses developed severe colitis (one fatal). Clostridium difficile was isolated from one of the horses, whereas no specific pathogens were isolated from the other. Both horses had typical changes in blood parameters seen in acute colitis. Clostridium difficile was also isolated from the faeces of a third horse given an even lower dosage of erythromycin in combination with rifampicin. This horse developed very mild clinical symptoms and recovered spontaneously. In the fourth horse given erythromycin only, very high numbers of Clostridium perfringens were isolated. The horses given rifampicin only did not develop any clinical symptoms and there were no major changes in their faecal flora. In conclusion, it has been demonstrated that low dosages of erythromycin ethylsuccinate can induce severe colitis in horses associated with major changes of the intestinal microflora. Clostridium difficile has been demonstrated as a potential aetiological agent in antibiotic-induced acute colitis.

Actinomycetales Infections↗

Cardio-respiratory and plasma lactate responses to exercise with low draught resistances in standardbred trotters.

Five Standardbred trotters performed treadmill exercise with incrementally increasing trotting velocities for 2 min intervals in three different tests until fatigue. Each test was performed with draught loads of either 10, 20 or 30 kilopond (kp). Each trotting interval was followed by 2 min periods at a walk without draught load. Recordings were made of heart rate (HR), respiratory rate (RR), plasma lactate (PLA) and stride frequency (SF) at the end of each trotting interval. The HR increased to average values of 191 +/- 10,203 +/- 10 and 214 +/- 7 bpm and PLA increased to 3.8 +/- 0.7, 7.3 +/- 3.8 and 10.8 +/- 6.4 mmol/l at 9 m/s in the three tests, respectively. The HR response to exercise was significantly higher with increasing draught loads, and PLA was significantly higher with 30 kp compared to 10 kp draught resistance. The lowest respiratory rate was seen in the test with 30 kp loading. Peak oxygen uptake (VO2peak) was measured in a separate test on a sloped treadmill with increasing velocities without draught load and averaged 70.4 +/- 9.11/min. Muscle biopsies were taken from the gluteus muscle. Individual variations were seen in VO2peak, muscle fibre composition and HR and PLA responses to exercise. In conclusion, at a certain velocity a small increase in draught resistance from 10 to 30 kp significantly increases both the HR and PLA responses. At comparable work intensities the horses differed in circulatory and metabolic responses to exercise.

Animals↗

Strategies for voluntary rehydration in horses during endurance exercise.

To avoid dehydration and a decrease in performance capacity in horses, fluid and electrolyte losses need to be compensated for during long distance rides as well as on other occasions when sweat losses are high during exercise. Thirteen endurance-trained horses, age 5-14 years, were used to compare 3 strategies of voluntary rehydration during prolonged exercise, offering 1) water, 2) water after administering salt paste (3 x 30 g of NaCl) per os and 3) 0.9% saline. The ride covered 62 km and consisted of 3 rounds, of 20, 22 and 20 km, respectively. During the first 20 km, no fluid was offered to any of the horses. Thereafter, fluid was repeatedly offered from buckets at the 'vet gates' and at fluid stations situated in the middle of the rounds. Fluid intake and bodyweight were measured during the ride and up until 3 b after the ride. The low heart rates and unchanged plasma glucose concentration indicated that the work load was moderate. Total fluid intake was significantly higher in the saline group than in the water group or the salt paste group. The total plasma protein concentration (TPP) fell below resting values in the saline group post exercise, indicating an increase in plasma volume. No changes in TPP were seen in the other groups. Plasma sodium concentration during the ride increased in the salt paste group but not in the saline drinking horses despite their higher NaCl intake. The water group had an increased plasma aldosterone concentration post exercise, indicating that sodium-conserving mechanisms had been activated. Plasma potassium concentration decreased in all treatments from pre- to post ride. It was concluded, that drinking saline solution during and after exercise is a good strategy for rehydration since this group showed the fastest recovery of their bodyweight losses. The persistently elevated plasma sodium concentration in the salt paste group during the ride, is indicative of a disturbance in the fluid distribution between the body fluid compartments, which can be exacerbated by the low water intake. To give salt paste immediately before or during exercise is, therefore, not recommended.

Administration, Oral↗

Hyaluronan turnover in the synovial fluid in metacarpophalangeal--and middle carpal joints in standardbred horses.

The biological turnover of hyaluronan (sodium hyaluronate) of different molecular weights (0.6 x 10(6) and 2.5 x 10(6) Daltons) was studied in the synovial fluid of the middle carpal and metacarpophalangeal joints of 6 clinically healthy Standardbred horses. The hyaluronan was radioactively labelled with 14C. The biological half-life (t1/2) was calculated from repeated synovial samples after injection of the labelled hyaluronan. The mean t1/2 in the metacarpophalangeal joints was 9.7 h for low molecular weight hyaluronan and 8.9 h for high molecular weight hyaluronan and in the middle carpal joints 16.0 h and 12.5 h respectively. These was no significant difference in turnover of the different molecular weights of hyaluronan.

Animals↗

Ischemic heart disease--major cause of death and graft loss after renal transplantation in Scandinavia.

Causes of graft loss and death were studied in 1347 recipients of primary renal transplants followed for 5 years after transplantation irrespective of graft function. Immunosuppression consisted of high or medium dose CsA and prednisolone or low dose CsA and prednisolone and azathioprine. In recipients of cadaver grafts, death with a functioning transplant was more common than graft rejection after the first posttransplant year, accounting for 49% and 41% of the graft losses, respectively. Of deaths with a functioning graft, 53% were due to ischemic heart disease (IHD) and 10% were due to other vascular disease. In the 55- to 64-year-old age group, the risk of death from IHD was 6.4 times higher in the transplanted nondiabetic patients, 8.6 times higher in the dialysis patients (European Dialysis and Transplant Association figures), and 20.8 times higher in the transplanted diabetic patients than in the general population (national figures). A multivariate Cox regression analysis showed that old age, diabetes mellitus, occurrence of acute rejection, pretransplant transfusions, delayed onset of graft function, and male gender were significant for death in IHD. We conclude that, in comparison to reports from other regions, Scandinavian renal transplant recipients are at high risk of dying of IHD. Future advances in long-term renal graft survival will depend largely on the success of preventing myocardial infarction and death in this patient population.

Adult↗