Biomedical subjects

A Stenström

Publications and source records attributed to A Stenström.

At least 19 recordsLinked to original sources

PubMed1999

Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen.

The endogenous cannabimimetic anandamide is hydrolyzed by a fatty acid amide hydrolase to yield arachidonic acid and ethanolamine. In the present study, the regional distribution of the activity and its sensitivity to inhibition by the enantiomers of ibuprofen, ketorolac, and flurbiprofen has been investigated. The rate of [3H]anandamide hydrolysis was found in both 7-week-old and 90-week-old rats to be in the order hippocampus > cerebral cortex > cerebellum > striatum approximately midbrain, with higher rates of hydrolysis for the 7-week-old rats than for the 90-week-old rats. In whole brain (minus cerebellum), the R(-)-enantiomer of ibuprofen was a mixed-type inhibitor of anandamide hydrolysis and was approximately 2-3 times more potent than the S(+)-enantiomer, IC50 values of 230 and 750 microM, respectively, being found. A similar pattern of inhibition of anandamide hydrolysis was seen when intact C6 rat glioma cells were used. Ketorolac inhibited rat brain anandamide hydrolysis, with IC50 values of 50, 440, and 80 microM being found for the R-, S-, and R,S-forms, respectively. The IC50 value for R-flurbiprofen (60 microM) was similar to the IC50 value for the S-enantiomer (50 microM). These data demonstrate that there is no dramatic enantiomeric selectivity of NSAID compounds as inhibitors of fatty acid amide hydrolase enzyme(s) responsible for the hydrolysis of anandamide. The enantiomers of flurbiprofen and R-ketorolac are the most potent NSAID inhibitors of fatty acid amide hydrolase yet reported.

Aging↗

PubMed1998

Long-term prognosis after healed amputation in patients with diabetes.

In this prospective study, mortality, rehabilitation, and new amputations on the same or on the contralateral leg were studied in 189 patients with diabetes who had achieved healing of an index amputation. Ninety-three patients had achieved healing after an index minor (below the ankle) and 96 after an index major (above the ankle) amputation, precipitated by a foot ulcer. The healing time was 29 weeks (range, 3-191 weeks) with a minor amputation and 8 weeks (range, 3-104 weeks) with a primary major amputation. The mortality 1, 3, and 5 years after the index amputation was 15%, 38%, and 68%, respectively, and was higher in patients who had achieved healing after major amputation than in patients achieving healing after minor amputation. The rate of new amputations after 1, 3, and 5 years of observation was 14%, 30%, and 49%, respectively. There was no difference among patients with an index minor and those with an index major amputation. The rate of new major amputations was 9%, 13%, and 23%, respectively, and was higher in patients with an index major amputation. Eighty-five percent of new amputations were precipitated by a foot ulcer. Patients living independently before the index amputation returned to living independently more often after a minor than a major amputation (93% versus 61%). One year after the index amputation, 70% of patients who had achieved healing after having a minor amputation and who could walk 1 km or more before amputation had regained this walking capacity, compared with 19% of patients having a major amputation. Seventy percent of patients with an index transtibial amputation who could walk before amputation were fitted with a prosthesis, and 52% were using it regularly. Patients with diabetes who had an index major amputation had a higher mortality, an equal rate of new amputation, and a lower rehabilitation potential than did patients who had an index minor amputation.

Adult↗

PubMed1997

Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide.

A measure of the metabolism of anandamide, an endogenous cannabimimetic agent, by rat cerebellar membrane preparations was obtained by following the time-dependent reduction in potency of this compound towards inhibition of binding of the high-affinity cannabinoid agonist ligand [3H]WIN 55212-2 to cannabinoid receptors. Thus for example, incubation of the membranes with 100 nM anandamide for 0, 10 and 30 min. prior to addition of [3H]WIN 55212-2 and phenylmethylsulphonyl fluoride (to inhibit the activity of anandamide amidase, thereby blocking further anandamide metabolism during the binding assay) produced 57 +/- 3, 38 +/- 5 and 19 +/- 7% inhibition, respectively, of [3H]WIN 55212-2 binding. This time-dependent effect was blocked by ibuprofen but not by acetyl salicylic acid, sulindac, acetaminophen or to any significant extent by ketoprofen and naproxen. Preliminary experiments using a direct assay of anandamide amidase with [14C]anandamide as ligand gave an IC50 value for ibuprofen of approximately 400 microM. The potency of ibuprofen as an inhibitor of anandamide metabolism was of the same order of magnitude as required for inhibition of cyclooxygenase-2 in cell-free systems and of the peak plasma concentrations of this drug following a 2 x 200 mg dose regimen. It is concluded that following therapeutic doses of ibuprofen, the metabolism of anandamide may be affected.

Acetaminophen↗

PubMed1997

Clinical characteristics and outcome in 223 diabetic patients with deep foot infections.

Clinical characteristics and outcome in 223 consecutive diabetic patients with deep foot infections are reported. Patients were treated by a multidisciplinary diabetic foot-care team at the University Hospital, Lund, Sweden, and were prospectively followed until healing or death. About 50% of patients lacked clinical signs of infection, such as a body temperature > 37.8 degrees C, a sedimentation rate > 70 mm/hour, and white blood cell count (WBC) > 10 x 10(9)/liter. Eighty-six percent had surgery before healing or death. Thirty-nine percent healed without amputation; 34% healed after a minor and 8% after a major amputation. Sixteen percent were unhealed at death, and 3% were unhealed at the end of the observation period. Of those unhealed at death or follow-up, 4 patients had had a major and 11 a minor amputation. After correction for age and sex, duration of diabetes < 14 years, palpable popliteal pulse, a toe pressure > 45 mmHg, and an ankle pressure > 80 mm Hg, absence of exposed bone and a white blood cell count < 12 x 10(9)/liter were all related to healing without amputation in a logistic regression analysis. We conclude that although only 1 in 10 had a major amputation, nearly all diabetic patients with a deep foot infection needed surgery and more than one third had a minor amputation before healing or death in spite of a well-functioning diabetic foot-care team responsible for all included patients.

Adult↗

PubMed1997

Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologically relevant concentrations. Mode of inhibition and structure-activity relationship.

The ability of rat brain (minus cerebellum) homogenates to deamidate arachidonyl ethanolamide (anandamide) was determined with a custom-synthesized substrate, arachidonyl ethanolamide-[1-3H] ([3H]anandamide). Conditions whereby initial velocities were measured were established. The homogenates deamidated anandamide with a Km value of 0.8 microM and a Vmax value of 1.73 nmol . (mg protein)-1 . min-1. The deamidation of 2 microM -3H-anandamide was inhibited by phenylmethylsulfonyl fluoride and arachidonyl trifluoromethyl ketone with IC50 values of 3.7 and 0.23 microM, respectively. Ibuprofen inhibited anandamide deamidation in a mixed fashion, with Ki and K'i values of 82 and 1420 microM. At an anandamide concentration of 2 microM, the IC50 values (in microM) of a series of compounds related in structure to ibuprofen were as follows: suprofen, 170; ibuprofen, 270; fenoprofen, 480; naproxen, 550; ketoprofen, 650; diclofenac, approximately 1000. Sulindac produced 27% inhibition at a concentration of 1000 microM, whereas isobutyric acid, hydrocinnamic acid, acetylsalicylic acid and acetaminophen were essentially inactive at concentrations </= 1 mM. We conclude that ibuprofen inhibits anandamide deamidation at pharmacologically relevant concentrations and that there is some specificity to the inhibition produced by ibuprofen and suprofen.

Animals↗

PubMed1995

Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach?

The purpose of this retrospective study was to evaluate the changes in diabetes-related lower extremity amputations following the implementation of a multidisciplinary programme for prevention and treatment of diabetic foot ulcers in a 0.2 million population with a 2.4% prevalence of diabetes. All diabetes-related primary amputations from toe to hip from 1 January 1982 to 31 December 1993 were included. In 294 diabetic patients, 387 primary major (above the ankle) or minor (through or below the ankle) amputations were performed, constituting 48% of all lower extremity amputations. The annual number of amputations at all levels decreased from 38 to 21, equalling a decrease of incidence from 19.1 to 9.4/100,000 inhabitants (p = 0.001). The incidence of major amputations decreased by 78% from 16/1 to 3.6/100,000 inhabitants (p < 0.001). The absolute number of amputations with a final level below the ankle showed no increase, but their proportion increased from 28 to 53% (p < 0.001) and the reamputation rate decreased from 36 to 22% (p < 0.05) between the first and last 3-year period. Thus, a substantial long-term decrease in the incidence of major amputations was seen as well as a decrease in the total incidence of amputations in diabetic patients. Seventy-one per cent of the amputations were precipitated by a foot ulcer. These findings indicate that a multidisciplinary approach plays an important role to reduce and maintain a low incidence of major amputations in diabetic patients.

Adult↗

PubMed1995

Clinical characteristics in relation to final amputation level in diabetic patients with foot ulcers: a prospective study of healing below or above the ankle in 187 patients.

The aim of this study was to describe the clinical characteristics in relation to final amputation level in diabetic patients with foot ulcers. In a prospective series, 187 consecutively presenting patients were investigated. From admission until final outcome, the patients were treated by a multidisciplinary team both as in- and out-patients. All the patients had one or more signs of neuropathy and 171 had evidence of peripheral vascular disease. Healing with an amputation below the ankle occurred in 74 patients, 88 patients healed with an amputation above the ankle, and 25 patients died unhealed. Amputation above the ankle was associated with high age, living in an institution, a limited walking capacity, cerebrovascular disease, congestive heart failure, and a low hemoglobin level. Amputation below the ankle was associated with diabetes diagnosis before 30 years of age and diabetes duration. In conclusion, older age, history of cerebrovascular disease and low hemoglobin level are associated with above ankle amputation level in diabetic patients with foot ulcers. However, level selection cannot be based upon these factors only, since some patients at high age, with cerebrovascular disease or with a low hemoglobin value, healed with an amputation below the ankle. None of these factors per se should be taken as a cause to choose a primary amputation above the ankle, unless amputation is supported by the total clinical picture, including local characteristics, such as type and localization of ulcer, and signs of peripheral vascular disease. More attention should be paid to biological than to chronological age.

Adult↗

PubMed1995

Measuring hallux valgus: a comparison of conventional radiography and clinical parameters with regard to measurement accuracy.

To assess the repeatability and error of conventional x-ray measurements, intra- and interobserver evaluations of measurement accuracy were done on 20 preoperative and 40 postoperative (20 chevron and 20 proximal osteotomy) x-rays of hallux valgus patients. Standard x-rays showed an average interobserver error of measurement of 6.4 degrees for the hallux valgus angle, 5.4 degrees for the intermetatarsal angle, and 2.0 mm for the intermetatarsal distance. The intraobserver error did not differ greatly. The repeatability and error of two clinical measurements, ball circumference, and dorsal to plantar range of motion of the first metatarsophalangeal joint were evaluated for 20 healthy volunteers. The ball circumference had an average measurement error of 1.1 cm, whereas the dorsal and plantar range of motion of the great toe had an average measurement error of 12 degrees in dorsiflexion and 16 degrees in plantarflexion. In both clinical and radiographic parameters, linear measurements were more accurate than angular measurements. Although x-rays are of value in hallux valgus surgery, standard x-rays are less accurate than previously assumed. Small changes produced by osteotomies may be hidden by the postoperative measurement error. The results of hallux valgus surgery should primarily be evaluated clinically. When clinical and radiological evaluations are made, linear measurements may be preferable.

Female↗

PubMed1995

Measurement of the forefoot with roentgen stereophotogrammetry in hallux valgus surgery.

Eight hallux valgus patients were marked with tantalum markers in conjunction with hallux valgus surgery (seven proximal osteotomies and one chevron osteotomy). Changes on weightbearing before surgery as well as corrective changes after surgery were analyzed with roentgen stereophotogrammetry (RSA) and with standard x-rays. RSA is accurate to 0.6 degrees in rotational changes and 0.3 mm in translation. Weightbearing changes were inconsistent, and minimal with both standard x-rays and RSA. It was possible to analyze the correction at the osteotomy site with RSA. In half the cases, the correction measured by RSA corresponded with that measured with standard x-rays, within measurement error; in the other cases, RSA showed that the correction was of a different size or direction than that measured on standard x-rays. Corrective changes in hallux valgus surgery are complex, including angular and translational changes at several levels and in several joints in order to produce a clinical resultant. Rotational changes can be evaluated with RSA. Although RSA in an optimal situation is very accurate, it is still limited to a laboratory setting.

Female↗

PubMed1994

Effects of cyanide in vitro on the activity of monoamine oxidase in striatal tissue from rat and pig.

We have shown previously in the rat that lethal, acute cyanide intoxication dramatically decreased the levels of dopamine (DA) in the striatum, while the synthesis of DA was increased. The main brain metabolite of DA, homovanillic acid, was also diminished. However, the levels of the oxidatively deaminated metabolite of DA, 3,4-dihydroxyphenylacetic acid, were not significantly changed. In order to elucidate further these findings we examined the effects in vitro of sodium cyanide on rat and pig brain monoamine oxidase (MAO; EC 1.4.3.4). The MAO activity was measured radiochemically using [14C]5-hydroxytryptamine (5-HT; 100 microM), [14C]phenethylamine (PEA; 20 microM) and [14C]DA (100 microM) as substrates. The amounts of cyanide added were comparable to those tissue concentrations of cyanide usually considered to be fatal in rats. The effect of cyanide on MAO was immediate. In rat, as well as pig, striatal tissue we found that cyanide produced a dose-dependent increase in the activity of MAO-A (as measured with 5-HT), but not MAO-B (as measured with PEA). The change in MAO activity was also seen with DA as substrate (MAO-A and -B). Kinetic constants, Km and Vmax, were determined. In both rat and pig striatum the Vmax values for 5-HT were significantly increased, but the values for PEA were not affected. A significant decrease in the Km value for PEA was, however, found in the presence of high concentrations of cyanide.

Animals↗

PubMed1994

The diagnostic efficacy of magnetic resonance imaging and ultrasonography in Morton's neuroma: a radiological-surgical correlation.

All patients operated upon for Morton's neuroma during 1991 who were examined with both magnetic resonance imaging and ultrasonography were included in this prospective study. The object of the study was to evaluate the diagnostic value of these two modalities. The preoperative diagnosis was purely clinical. Histology confirmed surgical findings. A 0.3 T scanner was used for the magnetic resonance imaging, and a 7.5 MHz linear transducer was used for the ultrasonography. The study includes nine patients. Eight neuromas were found at surgery. Of these, only five were diagnosed with magnetic resonance imaging and three with ultrasonography. This indicates that false negative diagnoses are common. At present we find these modalities of little or no value, but, with improved equipment and experience, they may become valuable.

Adult↗

PubMed1994

Local signs and symptoms in relation to final amputation level in diabetic patients. A prospective study of 187 patients with foot ulcers.

Local signs and symptoms were evaluated in 187 consecutively presenting diabetic patients undergoing amputation for foot ulcers. From admission until final outcome the patients were treated by the same multidisciplinary team both as in- and out-patients. At the time of amputation, the types of lesions were superficial/deep ulcer (n 17), ulcer with deep infection, but without gangrene (n 40), and gangrene with or without infection (n 130). Healing after a minor amputation (below the ankle) occurred in 74 patients, while 88 patients healed after a major amputation (above the ankle), and 25 patients died before healing had occurred. Deep infection and presence of popliteal or pedal pulses were associated with healing after minor amputation and so were ulcers on the small toes, metatarsal head area and midfoot. Pain, progressive gangrene, intermittent claudication, and decubital and multiple ulcers were related to healing after major amputation. In a logistic regression analysis, pain, progressive gangrene and intermittent claudication remained. However, none of these factors excluded healing of a minor amputation and thus selection of amputation level in diabetic patients with foot ulcers cannot be based upon these factors exclusively.

Adult↗

PubMed1994

Chevron osteotomy for hallux valgus not improved by additional adductor tenotomy. A prospective, randomized study of 84 patients.

We investigated 106 feet in 84 patients in a prospective randomized series where the clinical and radiographic results of the original chevron osteotomy were compared to the same procedure with the addition of an adductor tenotomy in patients averaging 47 years of age and with a mean follow-up of 3 years. Clinically there was no difference in the satisfaction rate of the two groups, with 58 satisfied and partially satisfied in the 62 operated by chevron osteotomy alone, and 42 of 44 in the group where adductor tenotomy was added. The hallux valgus angle decreased by 7.5 degrees in the group operated with chevron osteotomy and by 9.8 degrees (P 0.04) when an adductor tenotomy was added. The major objective factor affecting satisfaction was the attainment of a decreased ball circumference, shown by the fact that dissatisfied patients had a greater postoperative ball circumference than both satisfied and partially satisfied patients, whereas there were no radiographic correlations to satisfaction. We cannot recommend adding adductor tenotomy to the chevron osteotomy.

Adolescent↗

PubMed1993

Effects of adrenergic and cholinergic stimulation on islet monoamine oxidase activity and insulin secretion in the mouse.

It has been shown that the pancreatic beta-cell monoamines are located in the secretory granules, and that they have an inhibitory influence on insulin secretion. Monoamines are inactivated by the enzyme, monoamine oxidase. We now studied in vivo the relation between adrenergic and cholinergic stimulation, insulin secretion and islet monoamine oxidase activity in the mouse. Monoamine oxidase was assayed with three different substrates, serotonin, dopamine and beta-phenylethylamine. The alpha 2-adrenoceptor agonist, clonidine, induced a moderate inhibition (12-18%) of islet monoamine oxidase activity, accompanied by reduced plasma insulin and elevated plasma glucose levels. The alpha 1-adrenoceptor agonist, phenylephrine, did not induce any changes in these parameters. A marked insulin release following the injection of a maximal dose of the beta 2-adrenoceptor agonist, terbutaline, was accompanied by an increase (30-50%) in islet monoamine oxidase activity. The largest increase in monoamine oxidase activity was observed with serotonin as substrate (50%). These effects on insulin secretion and monoamine oxidase activity could not be blocked by clonidine. Similarly, injection of the non-selective alpha-adrenoceptor agonist, adrenaline, which unlike clonidine does not penetrate the blood-brain barrier, had no effect on insulin release induced by a maximal dose of the nonselective beta-adrenoceptor agonist, isoprenaline. Adrenaline, however, markedly suppressed the insulin release induced by a maximal dose of glucose. Cholinergic muscarinic stimulation by a maximal insulin releasing dose of carbachol did not affect islet monoamine oxidase activity. The results suggest that beta 2-adrenoceptor stimulation of islet monoamine oxidase activity reduced the monoamine content and thereby facilitated the release of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1993

Glucose modulation of islet monoamine oxidase activity in lean and obese hyperglycemic mice.

Islet beta-cell monoamines are known to influence the insulin-releasing mechanisms. These amines are localized in the insulin-secretory granules and are inactivated by the enzyme monoamine oxidase (MAO), a hydrogen peroxide (H2O2)-generating enzyme. The activity of islet MAO may consequently be of importance for insulin secretion. In the present investigation, we studied the relation between islet MAO activity and plasma levels of insulin and glucose in obese (ob/ob) hyperglycemic mice and their lean littermates. In addition, the effect of glucose on the MAO activity of in vitro-cultured islets was studied. MAO activity was assayed with serotonin, dopamine (DA), and beta-phenylethylamine (PEA) as substrates. After an overnight fast in adult (age, 6 months) lean mice, islet MAO activity was increased by 35% to 70%. Plasma levels of glucose and insulin were markedly decreased as expected. However, fasting in adult obese mice either did not affect islet MAO activity (PEA and DA) or induced a slight decrease (serotonin) of approximately 25% (P < .05). Plasma glucose levels in adult obese mice were not significantly affected by the overnight fast. However, a correlation analysis based on individual adult obese mice (fed and fasted) showed a negative correlation between plasma glucose concentration and islet MAO activity with PEA (r = -.65, P < .02) and DA (r = -.66, P < .02), respectively. Further, a positive correlation (r = +.58, P < .05) was found between glucose level and islet MAO activity when using serotonin as substrate. There was no difference in islet MAO activity with PEA and DA as substrates in fed obese versus fed lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Influence of beta 2-adrenoceptor stimulation and glucose on islet monoamine oxidase activity and insulin secretory response in the mouse.

Changes in the content of monoamines such as dopamine (DA) and serotonin (5-HT) in the insulin granules are known to influence insulin release. The monoamines are inactivated by monoamine oxidase (MAO), a hydrogen peroxide-generating enzyme, which may be of importance for the redox state of the beta-cell. We studied the action of two different insulin secretagogues, the beta 2-adrenoceptor agonist terbutaline and glucose, on islet MAO activity and the plasma levels of insulin and glucose. MAO was assayed with 5-HT, DA, and beta-phenylethylamine as substrates. At 6 min (but not at 2 or 30 min) after terbutaline injection, marked increases of islet MAO activity and the plasma insulin levels were recorded. The plasma glucose levels were of the same magnitude at all time points. Injection of glucose moderately suppressed enzyme activity at 2 min. This occurred concomitantly with the peak increase in plasma levels of insulin and glucose. At 60 min, when the plasma levels of glucose and insulin were restored to basal, a slight increase in MAO activity was observed. At 2 min after injection of different doses of glucose mixed with a maximal dose of terbutaline, the insulin secretory response was either increased (submaximal glucose dose) or unaffected (maximal dose of glucose) by the beta 2-adrenoceptor stimulator. However, when a maximal dose of glucose was given at 6 min after terbutaline, i.e., when islet MAO activity was increased, the insulin response to glucose was suppressed. Starvation for 24 h induced an increase in islet MAO activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Distal blood pressure as a predictor for the level of amputation in diabetic patients with foot ulcer.

The predictive value of distal blood pressure measurements for the level of amputation was studied prospectively in 161 consecutive diabetic patients with foot ulcers. The patients were treated as outpatients except for periods of surgery and when complications requiring hospital care occurred. All patients were treated pre- and postoperatively by the same multidisciplinary foot care team. Either ankle or toe blood pressure measurement was available in 86% of the patients. Incompressible arteries, ulcer or gangrene at the measuring site, previous amputation, poor general condition, and an emergency situation were factors that excluded standardized ankle and toe blood pressure measurements in 24% and 27% of the patients, respectively. An absolute lower ankle pressure level of 50 mm Hg was found, below which a minor amputation was never sufficient to achieve healing. An ankle pressure below 75 mm Hg was seldom sufficient, and at or above that pressure level, the ankle pressure had no predictive value in this respect. At a toe pressure below 15 mm Hg, a minor amputation was seldom sufficient. Ankle and toe pressure indices gave no further information.

Adult↗

PubMed1992

The influence of metal backing in unicompartmental tibial component fixation. An in vivo roentgen stereophotogrammetric analysis of micromotion.

The fixation of the tibial component in 36 patients with conventionally cemented unicompartmental knee arthroplasties for femorotibial gonarthrosis was studied using roentgen stereophotogrammetric analysis (RSA). Twenty-four tibial components were all-polyethylene while 12 were metal-backed. The follow-up was for 6 years. Significant migration was detected for all cases but two and ranged from 0.3 mm to 5.4 mm. The greater part of the migration occurred during the first 1-2 years, after which two-thirds of the prostheses remained stable. Seven all-polyethylene components were subjected to a stress examination after 1-2 years and displacement, induced by external forces, was found in all seven. A strong correlation was found between the extension of the radiolucent line and the migration. Otherwise, neither demographic, clinical, nor radiographic data correlated with the RSA results. In this study metal backing did not have any influence on prosthetic fixation as measured by RSA.

Aged↗