Is buprenorphine transdermal patch equally safe and effective in younger and elderly patients with osteoarthritis-related pain? Results of an age-group controlled study.

OBJECTIVE: A recent pharmacokinetic study with buprenorphine transdermal patches showed similar systemic exposures of buprenorphine in subjects aged ≥75 and 50-60 years. The current prospective, open-label study aimed to verify this in a clinical setting by evaluating efficacy and safety of buprenorphine patches in patients with chronic osteoarthritis (OA) pain. METHODS: Patients with chronic, moderate to severe osteoarthritic pain (hip and/or knee) were enrolled: 50-60 years (younger group, N = 65) and ≥75 years (elderly group, N = 57). After 2 weeks on paracetamol only, patients received buprenorphine patches (5-40 µg/h) for 12 weeks. Paracetamol rescue was provided. Primary endpoint was the Box-Scale-11 (BS-11) score for pain on average over the last week. WOMAC OA Index, EQ-5D, Patients' and Investigators' Global Assessment of Pain Relief, rescue medication use, sleep disturbance and quality of sleep were secondary efficacy endpoints. RESULTS: Both groups showed a statistically significant (p < 0.0001) and clinically relevant change from baseline to last visit in BS-11 score, with no significant difference between groups. The least squares (LS) mean change from baseline was 2.20 in elderly and 1.87 in younger patients, with an age group difference of 0.33 (95% CI: -0.42, 1.07). Non-inferiority of the elderly versus the younger group was shown. Both age groups showed a significant improvement in WOMAC total score, patients' overall health state (EQ-5D visual analogue scale) and sleep quality, and a significant reduction in rescue use and nights woken due to pain, with no significant differences between groups. Elderly patients tolerated buprenorphine patches at least as well as younger patients. CONCLUSIONS: Efficacy and tolerability of buprenorphine patches was demonstrated in chronic pain patients, regardless of age, supporting the conclusion that no age-related dose adjustment of transdermal buprenorphine is needed. A study limitation is lack of active control but no other opioid was appropriate in elderly patients or this indication.

Differential effect on cell-mediated immunity in human volunteers after intake of different lactobacilli.

Probiotics are live microorganisms which have beneficial effects on the host when ingested in adequate amounts. Probiotic bacteria may stimulate immune effector functions in a strain-specific manner. In this blind placebo-controlled trial, we investigated the effects on the immune system following daily intake of six different strains of lactobacilli or the Gram-negative bacterium Pseudomonas lundensis for 2 or 5 weeks. Blood lymphocyte subsets were quantified by fluorescence activated cell sorter and the expression of activation and memory markers was determined. The bacterial strains were also examined for their capacity to adhere to human intestinal cells and to be phagocytosed by human peripheral blood mononuclear cells. Intake of Lactobacillus plantarum strain 299v increased the expression of the activation marker CD25 (P = 0·01) on CD8(+) T cells and the memory cell marker CD45RO on CD4(+) T cells (P = 0·03), whereas intake of L. paracasei tended to expand the natural killer T (NK T) cell population (P = 0·06). The phagocytic activity of granulocytes was increased following intake of L. plantarum 299v, L. plantarum HEAL, L. paracasei or L. fermentum. In contrast, ingestion of L. rhamnosus decreased the expression of CD25 and CD45RO significantly within the CD4(+) cell population. The observed immune effects after in-vivo administration of the probiotic bacteria could not be predicted by either their adherence capacity or the in-vitro-induced cytokine production. The stimulation of CD8(+) T cells and NK T cells suggests that intake of probiotic bacteria may enhance the immune defence against, e.g. viral infections or tumours.

Limited gene flow may enhance adaptation to local optima in isolated populations of the Roesel's bush cricket (Metrioptera roeselii).

Variation in morphological traits along latitudinal gradients often manifests as size clines. In insects, both positive and negative correlations are seen, and the mechanism behind the response is unclear. We studied variation in seven morphological traits of Roesel's bush cricket, Metrioptera roeselii, sampled from seven latitude-matched-pair populations that were either geographically isolated from or connected to the species continuous distribution range. The aim was to examine whether morphological traits differed between isolated and continuous populations, and whether latitudinal variation was apparent. The data were used to indicate whether variation in trait means originates from plastic responses to the environment or genetic adaptation to local conditions. To evaluate the influence of gene flow on trait means, we analysed the genetic variation in seven microsatellites. Data showed that individuals from isolated populations display a positive relationship between latitude and body size, whereas individuals from continuous populations show little or no such relationship. The combined morphological and genetic data suggest that the isolated populations have adapted to local optima, while gene flow between continuous populations appears to counteract this process.

Aspergillosis in a North Island robin (Petroica longipes).

CASE HISTORY: A 3-year-old female North Island robin (Petroica longipes) was found dead on Tiritiri Matangi Island during the breeding season. CLINICAL FINDINGS: The bird was in poor condition, and there was a 13 x 8 mm granulomatous mass in the thoracic cavity causing displacement of the heart and left lung. Histologically, the mass was a large granuloma infiltrated with fungal hyphae, and the liver contained multifocal aggregates of inflammatory cells. DIAGNOSIS: Thoracic aspergillosis and multifocal hepatitis. CLINICAL RELEVANCE: Determining the causes of death in populations of wild birds is often hampered by a lack of recovery of carcasses, autolysis and poor clinical history. In this case, the life history of the bird was known and recovery of the body was relatively swift. This is the first published description of aspergillosis in a free-living North Island robin.

Influence of a drink containing different antioxidants and Lactobacillus plantarum 299v on plasma total antioxidant capacity, selenium status and faecal microbial flora.

The aim of the study was to investigate whether a supplement of antioxidants to subjects with a high working pace can influence the antioxidant capacity. The study was parallel and double blind with 98 subjects randomised into two groups. One of the groups was given a test drink with antioxidants for 4 weeks (450 ml/day) while the other group took a corresponding amount of placebo drink. The test drink contained: 2 mg beta-carotene/100 ml, 40 mg alpha-tocopherol/100 ml, 80 mg ascorbic acid/100 ml, 2 mg pyridoxine/100 ml, 15 mg magnesium/100 ml, 0.2 mg manganese/100 ml, 1 mg zinc/100 ml, 0.1 mg copper/100 ml and 10 microg selenium/100 ml. Consumption of the test drink for 4 weeks increased the total plasma antioxidant capacity by 7% (ferric reducing ability of plasma method, P<0.05 compared with the placebo group), and the content of selenium and selenoprotein P in serum was raised by 16-17% (P<0.001 compared with the placebo group). No significant changes were found in the placebo group. The test drink also contained Lactobacillus plantarum 299v (5 x 10(7) cfu/ml) and 4 weeks' consumption led to a significant increase of Lb. plantarum 299v in the faeces. In conclusion, consumption of a drink rich in different antioxidants can increase the antioxidant capacity in subjects with a high working pace. This can be valuable since it may increase the protection against reactive oxygen radicals.

Capsular contracture around saline-filled fine textured and smooth mammary implants: a prospective 7.5-year follow-up.

In a previous prospective randomized clinical study comparing in the same patient textured and smooth saline-filled mammary implants (Biocell) with large pore size (300 to 600 microm), we saw no difference in capsular contracture. This study was undertaken in a similar way to compare capsular contracture around smooth and textured saline-filled prostheses with pores of small size. During a period of 7.5 years, the breast hardness was followed up, and at the end of the study patient satisfaction was evaluated. Twenty healthy women with a mean age of 30 years were operated on for breast augmentation. Two surgeons performed all operations in a standardized way. Each patient received subglandularly a Siltex textured saline-filled prosthesis with a pore size of 30 to 70 microm in one breast, and a smooth saline-filled prosthesis in the other. The hardness of the breasts was evaluated after 0.5, 1, and 7.5 years using Baker grading and applanation tonometry. Eighteen patients completed 1-year and 7.5-year follow-up. Two breasts with smooth prostheses were contracted after 6 months (Baker III or IV). After 1 year, four patients with smooth prostheses and one with a textured prosthesis had capsular contracture (p = 0.34). Seven and one-half years after surgery, six patents with smooth and four with textured implants had contracture (p = 0.66). On two patients with smooth prostheses and one patient with a textured prosthesis, the capsule around the implant hardened between 6 and 12 months. Between 1 year and 7.5 years, three breasts with smooth and textured implants contracted and one with a textured implant softened.The patients reported on a Visual Analogue Scale (1 to 10) the impact of the augmentation on their quality of life to be 9 +/- 1. Four patients preferred the breast with the smooth prosthesis, three preferred the breast with the textured prosthesis, and the others found both breasts equal. This study showed no significant difference of contracture with smooth versus fine textured implants. The majority of the patients preferred the smooth implants. The patients reported that the breast augmentation had had an extremely high impact on their quality of life.

Miniaturised ultrasonic aspiration handpiece for increased applicability.

OBJECTIVE: At present, ultrasonic aspiration is routinely used in several fields of surgery, especially in brain and spinal micro-surgery for tumour removal. In order to broaden the access to difficult surgical sites, it is important to design highly miniaturised but still efficient handpieces. The internal resonant system, always made of high-grade materials, must be optimally dimensioned. Normally this is done semi-empirically, by successively improving the design during many iterative test steps. This method however involves several additional difficulties when the degree of miniaturisation increases. For example, small transducer weights exacerbate heat-dissipation problems and make design optimisation important. METHODS: To resolve these problems we have produced modelling software that makes it possible to simulate and automatically tune each individual interacting section of the design before it is actually manufactured, thereby assuring optimal efficiency. RESULTS: Using a new mini-handpiece, designed via the software, two cases of dissection of acoustic neurinomas were successfully performed. CONCLUSION: Using conventional physical steps for improving ultrasonic aspiration handpieces, several problems arise when the grade of miniaturisation increases, due to increasing demands. We have designed computer software for handpiece simulation. Using this model it has been possible to manufacture a highly efficient miniaturised handpiece.

Survival of Lactobacillus plantarum DSM 9843 (299v), and effect on the short-chain fatty acid content of faeces after ingestion of a rose-hip drink with fermented oats.

In a controlled and randomised double-blind study, 26 healthy adult volunteers consumed, for 21 d, 400 ml of a rose-hip drink containing oats (0.7 g/100ml) fermented with Lactobacillus plantarum DSM 9843 (RHL; containing 5 x 10(7) cfu ml(-1)), and 22 volunteers in a second group the same amount of a pure rose-hip drink (RH). Significant increases in the total faecal concentration of carboxylic acids (P < 0.05 after 1 week and P < 0.01 after 3 weeks of intake), acetic acid (P < 0.01 after 3 weeks of intake) and propionic acid (P < 0.01 after 3 weeks of intake and P < 0.05 eight days after intake ceased) were recorded in the RHL group, indicating increased fermentation in the colon. In both groups a significant increase was obtained in the concentration of faecal lactic acid (P < 0.001 after 1 and 3 weeks of intake). No changes were seen in the concentration of faecal butyrate. The numbers of faecal bifidobacteria and lactobacilli increased significantly in both groups after 3 weeks of intake. Sulphite-reducing clostridia rapidly decreased in the group receiving the product with Lb. plantarum DSM 9843 after 1 week of intake, and then also in the pure rose-hip group after 3 weeks of intake. No changes were seen in the numbers of total anaerobes, gram-negative anaerobes or total aerobes during administration. Lb. plantarum DSM 9843 was recovered in faeces from all volunteers in the RHL group. Median amounts were 7.0 (5.0-8.8) log10 cfu g(-1) after one week of intake, and 6.7 (5.0-8.9) log10 cfu g(-1) after 3 weeks, respectively. The strain was still recovered from faeces of five volunteers 8 d after administration ceased (> 4.8 log10 cfu g(-1)). During the period of intake the volunteers in the RHL group experienced a significant increase in stool volume, a significant decrease in flatulence and slightly softer stools. Volunteers in the RH group experienced a slight but significant decrease in stool volume.

Capsular contracture with textured versus smooth saline-filled implants for breast augmentation: a prospective clinical study.

Texturization of silicone-filled breast implants has been shown to reduce the incidence of capsular contracture. A double-blind clinical study was undertaken to compare this incidence in saline-filled implants with textured or with smooth surfaces. Twenty-one women underwent mammary augmentation with a textured implant in one breast and a smooth implant in the other. The implants were placed subglandularly. All operations were performed by the same surgeon and all follow-up examinations by another. Breast hardness was evaluated 6 months postoperatively with applanation tonometry, using Baker's grading, and after 12 months, now also with a questionnaire concerning the patient's evaluation. Capsular contracture (Baker 3) had occurred in 33 percent of the breasts at the end of the study, and was bilateral in five cases. The incidence of contracture and the patients' views on the results did not differ between textured and smooth prostheses or between right and left breasts. Five patients requested reoperation, two of them because of breast hardness. Texturization of saline-filled implants thus did not reduce the incidence of capsular contracture.

The mini bottle brush--a new fastening device in cancellous bone.

A new design for bone implants, the bottle brush, was recently presented in a pilot study on marrow cavities in the femur of rabbits. In this study, the concept is further evaluated on a mini bottle brush. The fixture, 5 x 7 mm, with an implant shaft made of CP-titanium and bristles of nylon coated with sputtered titanium, was inserted into the cancellous bone of the medial femoral condyle in 15 adult rabbits. The titanium fixture was compared with a similar brush without the titanium sputtered surface. The animals were sacrificed after 4 months and the quantity and quality of bone integration were evaluated with pull-out tests and histological examination. In both parameters, the values were significantly higher for the titanium-sputtered brushes, with removal forces similar to titanium cylinders of the same size and with a bone-to-metal contact area of about 50%.

Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats.

It has increasingly been suggested that the short-chain fatty acids (SCFA) acetic, propionic and butyric acids, derived from colonic fermentation of dietary fibre and other indigestible carbohydrates, exert different physiological effects. Formation of propionic acid is discussed in terms of beneficial effects on glucose and cholesterol metabolism. The aim of the present study was to evaluate possible metabolic effects of propionic acid and to differentiate between effects mediated in the upper gastrointestinal tract and those mediated in the hind-gut. For this purpose, obese hyperinsulinaemic (fa/fa) rats were studied during a 19 d test period. Sodium propionate was either fed orally through the diet (1 g/d), or infused rectally (0.15 g/d) to animals given diets high in cholesterol (20 g/kg) and saturated fat (130 g/kg). At the end of the test period total liver cholesterol pools were 20% lower (P < 0.01) in rats given dietary or rectally infused propionate (481 and 484 mg respectively) compared with the control group (614 mg). This was due to lower liver weights (P < 0.05) in propionate-treated animals, 15.5 and 15.3 g, v. 18.2 g in the control group, and no differences were noted in hepatic cholesterol concentrations. The urinary glucose excretion was measured during days 15-19 and was found to be lower (P < 0.05) in rats fed with propionate (23 mg) compared with the control group or the group infused rectally (39 and 38 mg respectively). In addition, fasting plasma glucose concentrations decreased significantly (P < 0.05) over the test period. It is concluded that orally supplied propionate affects both glucose and cholesterol metabolism as judged from lowered urinary glucose excretion, fasting blood glucose and liver cholesterol pools. On the other hand, propionate administered to the hind-gut at a physiologically relevant level reduces the hepatic cholesterol pool.

Fat cylinder transplantation: an experimental comparative study of three different kinds of fat transplants.

In an experimental comparative study, fat cylinders harvested with a new instrument were compared with excised fat and aspirated fat. In 12 New Zealand White rabbits, fat grafts of about 1 ml were transplanted from the fat pad between the shoulders to the scalp and rear side of the ears by three different fat harvesting techniques. After 6 months, the change in the weight of each of the 36 specimens was measured. All specimens were freeze-cut after fixation and stained with Sudan IV, a fat-specific stain. They were examined under a light microscope and evaluated by computer-assisted image analysis. There was no statistical difference in the percentage change in weight between the excised fat and the fat cylinder groups (2 and 1 percent, respectively). For aspirated fat, however, the difference was significant (-59 percent). There also were significantly more surviving mature adipocytes in the fat cylinder group than in the aspirated fat group. We conclude that fat cylinders harvested with the new instrument are as good grafting material as excised fat, while aspirated fat in this study was clearly inferior for grafting.

Swedish midwives' awareness of, attitudes to and use of selected research findings.

Members of a county division of the Midwives' Association of Sweden were surveyed to examine their awareness of, attitudes to and use of selected research findings. A total of 14 findings from research within the midwifery field were identified from midwives' dissertations and the journal Jordemodern using the criterion of physical availability. Questionnaires were mailed according to the membership list (n = 146). The response rate was 74% (n = 118). The results demonstrated that 75% of the midwives were aware of research findings, 65% were convinced of their usefulness and 63% used findings at least sometimes. According to the stages of Rogers' innovation-decision model the midwives were in the 'persuasion' stage, which is consistent with the result in Brett's 1987 study. The results indicate that research findings are used when midwives believe that the findings provide good care for mothers and babies. Even though the midwife in Sweden is considered to be an independent practitioner she is a member of a limiting social system. With regard to the interests influencing the health care system there is a need to examine the innovation-decision process from an organizational perspective to effectively improve the quality of care.

The "bottle brush": a new concept for uncemented anchorage of bone implants. Preliminary mechanical and biomechanical studies.

We present a new concept for bone of implants, the "bottle brush". It may be suitable for joint prostheses, dental or percutaneous implants, or other devices fixed into bone. Mechanical pullout studies in artificial brass cavities of different sizes and shapes and implantation studies in 20 rabbits, have been successfully carried out. Further experimental and clinical studies are in progress.

Roentgenographic assessment of the hip-knee-ankle axis in medial gonarthrosis. A study of reproducibility.

A preoperative reliable recording of the knee alignment is necessary to calculate the correct wedge at high tibial osteotomy for medial gonarthrosis. To determine the reproducibility of the hip-knee-ankle angle (HKA), a preoperative, whole lower limb roentgenogram was obtained twice in eight patients, and each roentgenogram was judged by two radiologists. Assessment of the HKA had a variability of at most 2 degrees, which is highly significant for a reliable calculation of the wedge at tibial osteotomy.

Clinical experience with the Unilink/3M Precise microvascular anastomotic device.

The Unilink/3M Precise anastomotic device for microvascular anastomoses has been evaluated in 38 critical anastomoses in 26 selected patients. The microvascular anastomosis was usually completed within three minutes by a single surgeon. There was only one failure, when an arterial anastomosis clotted because of a technical error. In all patients tissue survival was dependent on patent mechanical anastomoses (critical anastomoses) and the follow-up period was more than three years.

Involvement of opioid mechanisms in peripheral motor control of detrusor muscle.

Isometric recordings of mechanical activity in muscle strips from rat and human detrusor were performed and the effect of mu- and delta-opioid receptor stimulation and blockade on detrusor contraction induced by electrical field stimulation was tested. Stimulation of the opioid mu-receptor with morphine (10(-13)-10(-4) M) and DAGO (10(-13)-10(-6) M) had no significant effect on electrical field stimulation except at one concentration of morphine (10(-6) M). Naloxone (10(-10)-10(-5) M) caused a significant facilitation of the electrical field stimulation-induced contraction, which was counteracted by morphine (10(-8) M) and the delta-agonist DPDPE (10(-8) M) in both rat and human detrusor. Addition of atropine (10(-6) M) or hexamethonium chloride (10(-6) M) or spantide (10(-6) M) did not alter the facilitating effect of naloxone in the rat detrusor. Hexamethonium (10(-5) M) decreased the facilitating effect of naloxone on electrical field stimulation-induced contractions in the human detrusor, indicating involvement of ganglionic mechanisms. In human detrusor about 15% of the contractile response was found to be atropine-resistant (10(-6) M) and one third of this was found to be resistant to tetrodotoxin (1.5 x 10(-6) M). The atropine resistant-response in human detrusor was facilitated by naloxone to the same extent as the atropine-sensitive part. Adrenergic blockade per se, achieved with phentolamine mesylate (10(-6) M) and propranolol (10(-6) M), caused a significant facilitation of the electrical field stimulation-induced contraction in the rat detrusor but did not affect the facilitating effect of naloxone (10(-13)-10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)