Effects of Lactobacillus reuteri-containing lozenges on healing after surgical removal of mandibular third molars: a randomised controlled trial.

We investigated the effect of probiotic supplements on oral wound healing, swelling, pain and discomfort after surgical removal of mandibular third molars. A second aim was to evaluate if the intervention could influence the concentrations of oxytocin in saliva. Sixty-four consecutive volunteers (18-34 years) were enrolled to a double-blind randomised placebo-controlled trial with two parallel arms. Following surgery, the patients were asked to take three lozenges per day containing two strains of Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo for two weeks. The clinical healing and extra-oral swelling were scored two weeks post-operatively. Samples of wound exudate were cultivated for the presence of Staphylococcus aureus and ß-haemolytic streptococci. Salivary oxytocin concentrations were analysed from pre- and post-surgery samples using ELISA technique. Compliance and the subjective perception of swelling, pain and discomfort were reported daily through visual analogue scales in a logbook. All patients except three completed the protocol and the postoperative course was uneventful in most cases. Minor extra-oral swellings were noted in five patients, but none required antibiotic treatment. At the 2-week follow-up, there were no significant differences in clinical wound healing index, extra-oral swelling, bacterial growth or salivary oxytocin levels between the groups. The self-reported data unveiled, however, a significantly reduced sense of swelling, in particular during the second week after surgery in the probiotic test group (P<0.05). Likewise, significantly fewer nights with disturbed sleep and fewer days with sick-leave from work were reported among the participants in the test group (P<0.05). No differences were found in the post-operative use of analgesics. In conclusion, we found no significant influence of probiotic supplements on objective wound healing after surgical extraction of impacted mandibular third molars. However, since the patients' perceived significant post-operative ameliorations, further studies are needed to explore the patient's value of the intervention.

Alarming spread of vancomycin resistant enterococci in Sweden since 2007.

The total number of persons infected or colonised with vancomycin-resistant enterococci mandatorily reported to the Swedish Institute for Infectious Disease Control increased dramatically during 2007 and 2008. During a period of twenty months from 1 July 2007 to 28 February 2009, a total of 760 cases were reported compared with 194 cases reported during the entire period from 2000 to 2006. This rise was mainly attributed to a wide dissemination of vancomycin resistant enterococci which started in a number of hospitals in Stockholm in the autumn of 2007 and was followed by dissemination in various healthcare facilities (hospitals and homes for the elderly) in a further two Swedish counties in 2008. The majority of the cases (97%) were acquired in Sweden and among these, healthcare-acquired E. faecium vanB dominated (n=634). The majority of these isolates had identical or closely related pulsed-field gel electrophoresis patterns indicating clonal dissemination in the affected counties. The median minimum inhibitory concentration of vancomycin was 32 mg/L (ranging from 4 to >128 mg/L) and of teichoplanin 0.12 mg/L (ranging from 0.06 to 0.25 mg/L). Particular emphasis was placed on countermeasures such as screening, contact tracing, cleaning procedures, education in accurate use of infection control practices as well as increasing awareness of hygiene among patients and visitors. With these measures the dissemination rate decreased substantially, but new infections with the E. faecium vanB strain were still detected.

Lack of effects of recombinant human GH on spermatogenesis in the adult cynomolgus monkey (Macaca fascicularis).

OBJECTIVE: The effects on male reproductive parameters after 1 year of treatment with recombinant human GH to the cynomolgus monkey were investigated. DESIGN: Twenty-four male cynomolgus monkeys were given daily subcutaneous doses of 0 (vehicle) (n=7), 0.4 (n=5), 2.0 (n=5) and 10.0 (n=7) IU/kg bodyweight for 52 weeks. At completion of the treatment period two control and two high-dose animals were left for a 12-week treatment-free period. METHODS: Before and during the treatment period and during the recovery period, sperm analyses, testicular volume measurements and hormone analyses of prolactin (PRL), LH, FSH, testosterone and IGF-I in serum, and analysis of serum antibodies against human GH were performed. Testicular morphology was monitored by biopsies, predose and on day 15 of the study, and with light microscopy on organ samples collected at time of death, at the end of the treatment, and during recovery periods respectively. RESULTS: Of all studied parameters, alterations were observed only in serum levels of IGF-I and PRL. IGF-I showed a dose-dependent increase throughout the treatment, with a normalisation during the treatment-free period. PRL decreased significantly in animals given 10.0IU/kg per day from week 14 of treatment and throughout the study but with a normalisation upon cessation of treatment. Spermatogenesis, as judged from semen analysis, testicular volume measurements and testicular morphology was not affected. CONCLUSION: This controlled preclinical study demonstrates that high doses of human GH do not alter male reproductive parameters in a non-human primate model.

Effects of very high doses of human growth hormone (hGH) on the male reproductive system in the dog.

The effects of very high doses of human growth hormone (hGH), pituitary derived or recombinant methionyl-hGH, on the morphology of reproductive organs and on some hormones in the male dog are described. The studies were part of a toxicological documentation of hGH. A total of 18 male dogs aged 7.5-20.5 months, from four studies were treated subcutaneously with hGH for 20-28 days at dose levels of 3, 10 or 25 IU kg-1 day-1 or 1 IU kg-1 three times weekly. Plasma levels of luteinizing hormone (LH), testosterone and prolactin were determined in one study. Organ weighing, macroscopic and histopathologic examinations of male reproductive organs at the end of the treatment period were included in all studies. Treatment with 25 IU kg-1 day-1 resulted in reduction of testis and prostate weights, degeneration of germ cells and epithelial atrophy in the testis, degenerative changes in epididymis and reduced height of the prostatic epithelium. Similar, although less severe morphological changes were observed after treatment with 10 IU kg-1 day-1. Treatment with 25 IU kg-1 day-1 also caused a marked reduction of plasma prolactin, LH and testosterone levels. These results suggest that repeated administration of very high doses of hGH interferes with the hormonal regulation of the testis in the dog.

Influence of left ventricular function on survival after coronary artery bypass grafting.

BACKGROUND: Preoperative left ventricular function is a most important predictor for survival in patients with ischemic heart disease. To elucidate the optimal timing of recommended coronary artery bypass grafting, we investigated the influence of different aspects of preoperative left ventricular function on relative survival. METHODS: To calculate the relative survival and estimate the disease-specific survival, we compared 6,514 patients who survived the first month after primary coronary artery bypass grafting with the general Swedish population stratified by age, sex, and 5-year calendar period. In particular we studied the relation between relative survival and different aspects of left ventricular performance, namely left ventricular function at rest, New York Heart Association functional class, and number of previous myocardial infarctions. RESULTS: The three variables (left ventricular function at rest, New York Heart Association functional class, and number of previous myocardial infarctions) as well as age and follow-up year gave independent information concerning relative survival. The results from this multivariate analysis were used to define a risk score for each patient. Patients were categorized into different risk groups. Patients in the low-risk group (30% of the total) showed a survival better than that of the population at large for 9 years after operation. The medium-risk group had no or low excess mortality for about 7 years, and the high-risk group (25%) showed increased excess mortality immediately after operation. CONCLUSIONS: If primary coronary artery bypass grafting is performed before the left ventricular function and physical performance deteriorate, survival is excellent.

Effects of insulin-like growth factor I (IGF-I) on the small intestine: a comparison between oral and subcutaneous administration in the weaned rat.

Several studies have suggested that growth factors play an important role in the development and the maintenance of the gastrointestinal tract. Colostrum and normal breast milk as well as intestinal secretion are reported to contain IGF-I. Thus, the objective of this study was to investigate whether the route of administration of IGF-I, subcutaneously and orally, was important for the way of influencing the gastrointestinal tract in the weaned rat and further to observe if this effect was affected by different feed regimens. Well nourished weaned rats subcutaneously administered IGF-I (2 mg/kg body weight and day during 14 days) were found to have significantly increased relative weights of the small intestine, increased duodenal crypt depths and villi heights compared with control rats. The same dose given orally in bovine milk had no effect. Furthermore, a study was performed with the same dose of IGF-I given for 7 days together with a restricted feed regimen. Similar observations, although of a slightly smaller magnitude, were found. These observations indicate that the effect of IGF-I on gastrointestinal renewal in the weaned rat is not depending on an IGF-I supply through the gastrointestinal fluids but rather through a supply via the circulation or by a local intestinal production. The effects were statistically significant both in well fed and malnourished conditions.

Magnetic resonance imaging as an aid to the diagnosis and treatment evaluation of suspected myocardial sarcoidosis in a fighter pilot.

We present a case of possible myocardial sarcoidosis suspected by the presence of multiorgan sarcoidosis along with cardiac dysrhythmia. The diagnosis of a highly probable sarcoid infiltrate was made by magnetic resonance imaging, depicting a high intensity mass in the ventricular septum. Following corticosteroid treatment the mass disappeared, and remains absent after 3 years followup. Also, only minor dysrhythmia has been observed during this period. The aeromedical implications are discussed.

Survival after coronary artery bypass grafting. Experience from 4661 patients.

The duration of the reduction of mortality after coronary artery bypass grafting (CABG) is an important issue and this study was undertaken to evaluate time in relation to excess mortality among CABG patients compared with the general population. Survival was analysed in 4661 patients who had undergone their first isolated CABG. Observed survival was related to that expected among subjects from the general Swedish population stratified by age, sex and 5-year calendar period, to calculate relative survival and estimate disease-specific survival. Relative survival (including all deaths) was 94.6% at 5 years, 82.5% at 10 years, and 59.9% at 15 years. A multivariate model based on relative survival rates adjusted for age, year of surgery, severity of coronary disease, left ventricular function, and smoking habits was used. Compared with the first year of follow-up, the relative hazard (a measure of the risk of death) was at a minimum 2 years after surgery, but was dramatically increased after about 8 years. Relative survival was worsened by smoking at the time of operation and by moderate or severe left ventricular dysfunction pre-operatively. The survival rate was higher among patients operated on after 1985 than among those operated on earlier.

Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography.

The relationship between regional oxidative and total rCMRglc in five healthy volunteers in activated and non-activated areas of the brain has been investigated with positron emission tomography (PET). The tracers [1-11C]-D-glucose and [2-18F]2-fluoro-2-deoxy-D-glucose were used. A previous study has shown that the former may be used to measure the rate of glucose oxidation while the latter tracer is used to measure the total rate of glucose consumption. Regional activation was performed (voluntary finger movements). Use of a computerized brain atlas enabled comparison between the regional oxidative and total rCMRglc in each volume element of the brain for the group of subjects. The values of total and oxidative rCMRglc, when calculated for each volume element of the brain and displayed in a scatter plot, were found to be symmetrically grouped around a straight line which passes close to the origin. The slope of this line varied between the subjects. This indicates that, on the average, the fraction of non-oxidative glucose utilization is constant within each subject, regardless of the value of rCMRglc and, further, that the fraction of non-oxidative glucose utilization varies between subjects. The total and oxidative CMRglc in the activated left hand area were 23.4 +/- 0.9% (mean +/- SEM) and 11.7 +/- 0.3%, respectively, higher than in the contralateral homologous non-activated area. Our interpretation of the difference is that regional activation increases the fraction of non-oxidative glucose consumption. This interpretation is supported by a previous PET study using [15O]O2, and by studies using MRS technique.

The transport of tyrosine into the human brain as determined with L-[1-11C]tyrosine and PET.

An alteration of dopaminergic transmission in the brain has been proposed for schizophrenia. To explore this, the rate constant for the intransport of L-tyrosine across the blood-brain barrier in healthy controls and in patients with schizophrenia (DSM-III-R) was determined with PET and L-[1-11C] tyrosine as the tracer. Kinetics for tyrosine transport were determined according to a two-compartment model using radioactivity data of arterial blood and brain tissue sampled between 1 and 3.5 min after a bolus injection of L-[1-11C] tyrosine. Radioactivity was measured every second in the blood and in 10-sec intervals in the brain tissue. In the normal controls the brain intransport rate constant for tyrosine was 0.052 ml/g/min with an influx rate of 2.97 nmol/g/min. The patients had a similar intransport rate constant (0.045 ml/g/min) but a lower influx rate of tyrosine 1.95 nmol/g/min (p less than 0.05). The patients' tyrosine concentrations in the blood were lower. For data sampled between 5 and 25 min, the net accumulation rate of tyrosine into the brain was 0.015 ml/g/min in the controls which did not differ to the patients' rate. However, the net utilization of tyrosine was lower in the patients (0.672 nmol/g/min) than in the controls (0.883 nmol/g/min) despite similar tissue concentrations of tyrosine.

Brain metabolism in Alzheimer's dementia: studies of 11C-deoxyglucose accumulation, CSF monoamine metabolites and neuropsychological test performance in patients and healthy subjects.

Thirteen patients with dementia of Alzheimer type and nine age-matched control subjects were examined by a battery of neuropsychological tests and by positron emission tomography (PET) with 11C-deoxyglucose as a tracer for regional glucose metabolism in the brain. Concentrations of the monoamine metabolites HVA, MHPG and 5-HIAA were determined in the CSF from patients and controls. In the patients there was a diminished glucose metabolism in posterior parietal and superior temporal cortex areas to 60% of control levels. Other cortical areas showed similar changes, whereas the pre- and postcentral area, the cerebellum, the hippocampus and the basal ganglia showed less or no change. The decline in cortical metabolism in the patients was symmetrical but the variation in the left/right ratio was greater than in the controls. The CSF levels of monoamine metabolites did not differ between patients and controls. High levels of the metabolites were associated with low rates of glucose metabolism, possibly due to inhibitory influences of monoaminergic pathways upon cortical and subcortical neurons. The rate of glucose metabolism correlated positively with the neuropsychological test performance in both patients and controls. Verbal and memory performances were associated with greater left hemisphere metabolism in the patients, but not in the controls, whereas non-verbal abilities tended to be associated with right hemisphere metabolic dominance.

Sensitivity to sensitins and tuberculin in Swedish children. I. A study of schoolchildren in an urban area.

Non-BCG-vaccinated schoolchildren (8 or 9 years of age) were simultaneously tested on separate arms with 2 IU PPD RT23 and 0.1 microgram Mycobacterium avium sensitin RS10 or 0.1 microgram Mycobacterium scrofulaceum sensitin RS95. None of the 2819 analysed children had any known exposure to tuberculosis. A total of 3.4% reacted with an induration greater than or equal to 6 mm to PPD RT23. Half the number of children were tested with M. avium sensitin and 25.4% reacted while the remaining were tested with M. scrofulaceum sensitin and 32.4% reacted when the cut-off was 6 mm. For about 90% of the children the sensitin reaction was larger than or equal to the tuberculin (PPD RT23) reaction. Correlation analyses showed that moderate and high PPD RT23 values were combined with still higher sensitin values, indicating that the tuberculin reactions were mainly cross-reactions due to the antigenic similarity between tuberculin and sensitins. The presence of birds, dogs and cats in the homes was combined with an increased frequency of children reacting to the sensitins used. The children with reactions to PPD RT23 greater than or equal to 6 mm were examined and chest X-rays were performed. None of them showed any signs or symptoms of mycobacterial disease. In non-BCG-vaccinated Swedish schoolchildren without clinical signs of tuberculosis and without known contact with a contagious tuberculous person, indurations less than 12 to 14 mm on tuberculin testing are probably caused by atypical mycobacteria. In such cases sensitin tests should be performed to verify the suspicion.

Effects of sulpiride and chlorpromazine on regional cerebral glucose metabolism in schizophrenic patients as determined by positron emission tomography.

Positron emission tomography (PET) was used to determine regional brain glucose metabolism in schizophrenic patients (n = 17) before and during neuroleptic treatment. The patients had not been treated with neuroleptics for at least 3 weeks before the first study. All suffered from acute psychotic symptoms and were hospitalized to obtain neuroleptic treatment. After determination of regional brain metabolism without neuroleptic treatment, 11 patients were treated with sulpiride (800 mg/day) and 6 patients were treated with chlorpromazine (400 mg/day) over 5-6 weeks before the second PET investigation. The control group consisted of seven healthy male volunteers, also investigated twice 5 weeks apart. The PET investigation was made with the subject in a resting state. The tracer was uniformly labelled 11C-glucose. The metabolism was determined bilaterally in 15 brain regions cortical, as well as central regions. Metabolic rates differed among the groups. The sulpiride group had lower metabolic rates than the controls and the schizophrenic patients later treated with chlorpromazine. The sulpiride group, in which absolute metabolic rates were determined, were clinically more autistic and chronic than the chlorpromazine group. It was proposed that these facts could explain the lower metabolic rates in the sulpiride group. A significant change in metabolism in relation to drug treatment was only found in one brain region. The selective D2-receptor antagonist sulpiride increased the metabolic rate in the right lentiform nucleus in comparison with the patients treated with chlorpromazine and the controls. Likewise, relative metabolic rates were increased only in the right lentiform nucleus. Negative correlations between intensity of clinical symptoms and metabolism indicated that emotional tone and drive were related to brain metabolism. No correlations were found between drug concentrations and metabolism or clinical symptoms.

Restricted lesions after testicular biopsies in young and adult rats.

In order to evaluate the possible harmful effects of surgical removal of a testicular biopsy, adult and immature rats were subjected to unilateral testicular biopsy and were studied 2-4 months later. One group of adult rats were sham-operated. Perfusion-fixed, plastic-embedded specimens of the testes were examined by light microscopy. No morphological differences were found between rats that were immature and those that were adult at the time of biopsy. The lesions observed were focal and occurred only in the vicinity of the site of biopsy. Only about 0.5% (range 0.01-4.5) of the testis was affected. No morphological signs of any immune reaction were observed. It is suggested that the lesions are caused mainly by interference with local blood flow, and to a minor extent by disruption of the flow of seminiferous tubule fluid.

The effect of ipratropium bromide on nasal hypersecretion induced by methacholine in patients with vasomotor rhinitis. A double-blind, cross-over, placebo-controlled and randomized dose-response study.

The effect of various doses of ipratropium bromide aerosol on nasal hypersecretion induced by five concentrations methacholine was studied in 24 patients with vasomotor rhinitis and excessive watery nasal secretion. The volume of nasal secretion was greater with each of the five increasing doses of methacholine from 7.5 to 120 mg/ml. The median volume of nasal secretion was alike in all patients after administration of methacholine only and after treatment by placebo followed by methacholine. When the patients were treated with ipratropium bromide prior to administering methacholine the volume of secretion was reduced significantly. With doses of 40 micrograms and 100 micrograms of ipratropium to each nostril a similar reduction in the volume of secretion occurred but a still greater reduction by the application of 200 micrograms of ipratropium when compared with treatment by the placebo. While the volume of secretion increased with each increasing concentration of methacholine, a similar pattern of reduced secretion for each concentration of methacholine was seen with each greater concentration of ipratropium. In patients with vasomotor rhinitis, treatment with ipratropium bromide was found to reduce significantly the hypersecretion induced by methacholine when compared with treatment by the placebo. This reduction was greater with greater doses of ipratropium.