Search PubMed⌕ Search

Biomedical subjects

S Akerman

Publications and source records attributed to S Akerman.

At least 37 records · Page 2Linked to original sources

GABA receptors modulate trigeminovascular nociceptive neurotransmission in the trigeminocervical complex.

1. GABA (gamma-aminobutyric acid) receptors involved in craniovascular nociceptive pathways were characterised by in vivo microiontophoresis of GABA receptor agonists and antagonists onto neurones in the trigeminocervical complex of the cat. 2. Extracellular recordings were made from neurones in the trigeminocervical complex activated by supramaximal electrical stimulation of superior sagittal sinus, which were subsequently stimulated with L-glutamate. 3. Cell firing evoked by microiontophoretic application of L-glutamate (n=30) was reversibly inhibited by GABA in every cell tested (n=19), the GABA(A) agonist muscimol (n=10) in all cells tested, or both where tested, but not by iontophoresis of either sodium or chloride ions at comparable ejection currents. Inhibited cells received wide dynamic range (WDR) or nociceptive specific input from cutaneous receptive fields on the face or forepaws. 4. The inhibition of trigeminal neurones by GABA or muscimol could be antagonized by the GABA(A) antagonist N-methylbicuculline, 1(S),9(R) in all but two cells tested (n=16), but not by the GABA(B) antagonist 2-hydroxysaclofen (n=11). 5. R(-)-baclofen, a GABA(B) agonist, inhibited the firing of three out of seven cells activated by L-glutamate. Where tested, this inhibition could be antagonized by 2-hydroxysaclofen. These baclofen-inhibited cells were characterized as having low threshold mechanoreceptor/WDR input. 6. GABA thus appears to modulate nociceptive input to the trigeminocervical complex mainly through GABA(A) receptors. GABA(A) receptors may therefore provide a target for the development of new therapeutic agents for primary headache disorders.

Animals↗

Attitudes to dental health and care among 20 to 25-year-old Swedes: results from a questionnaire.

During the last 3 decades, large resources have been allocated through the organized dental care system for the improvement of dental health among children and teenagers in Sweden. The aim of this study was to describe attitudes related to dental health and dental care among 20 to 25-year-old Swedes. A random sample of 650 individuals was drawn from the database of the National Social Insurance Board of Sweden. A postal questionnaire comprising 70 questions was delivered to the subjects and the response rate was 78%. A high proportion of the respondents considered themselves to have a high need for dental care. They had a strong conception of being able to influence their own dental health. Quite a few were concerned about their dental health. A high proportion indicated that they were satisfied with their dental function, but fewer individuals were satisfied with the appearance of their teeth. The respondents also reported good reception by their dentists, although opinions differed between the sexes. Women reported a significantly higher degree of discomfort and unease than men. Most respondents had adopted good oral hygiene habits but dental floss was rarely used. The majority of subjects indicated that they attended dental examinations on an annual basis. There is a need for further investigation into patients' attitudes to dental health and dental care. It is important to understand the significance patients attach to different concepts in the dental treatment. This would enhance our understanding of how the concept of felt need is expressed and transformed into demand for care.

Adult↗

Influence of ionic strength on drug adsorption onto and release from a poly(acrylic acid) grafted poly(vinylidene fluoride) membrane.

Ion exchange resins have several applications in pharmacy for controlled or sustained release of drugs. In the present study, effects of the ionic strengths of adsorption medium and dissolution medium on drug adsorption onto and release from a acrylic acid grafted poly(vinylidene fluoride) (PAA-PVDF) were studied. Despite their porosity, PAA-PVDF membranes act reasonable well as cation exchange membranes. It was observed, that ionic strength of adsorption medium, degree of grafting and concentration of propranolol-HCl in adsorption medium affect propranolol-HCl adsorption onto the membrane. The fluxes of smaller molecules (MW < 500) across the membrane decreased with ionic strength of buffer solution, whereas the fluxes of the large molecules (FITC-dextran, MW 4400) increased with ionic strength. Release rate of adsorbed propranolol-HCl from the membrane into phosphate buffer was greatly affected by ionic strength of adsorption medium. These results can be explained by a cation exchange process between membrane and cations present in the buffer solution and swelling behavior of the grafted PAA chains.

Acrylates↗

Drug release from a porous ion-exchange membrane in vitro.

The effect of environmental ionic strength on the rate of drug release from a cation exchange membrane was evaluated. Cationic propranolol-HCl, timolol, sotalol-HCl, atenolol and dexmedetomidine-HCl and neutral diazepam were adsorbed onto a porous poly(vinylidene fluoride) (PVDF) membrane that was grafted with bioadhesive poly(acrylic acid) chains (PAA-PVDF). Despite its porosity, the PAA-PVDF membrane acted as a cation exchange membrane. The release of adsorbed drug from the PAA-PVDF membrane was investigated by using a USP rotating basket apparatus. Adsorption of cationic drugs onto the PAA-PVDF membrane tended to increase with increasing lipophilicity of the drug. A decrease in the ionic strength of the adsorption medium increased the amount of the cationic drugs adsorbed onto the membrane, but had no effect on diazepam adsorption. The release of cationic drugs from the PAA-PVDF membrane was greatly affected by the ionic strength of both the adsorption medium and the dissolution medium, while ionic strengths did not affect diazepam release. Our results suggest that the ionic strength of both the adsorption and dissolution media substantially affects the release rate of a drug that has been adsorbed onto the ion exchange membrane, primarily via electrostatic interactions, while ionic strength has no effect on the release of a drug which has been adsorbed onto the membrane via non-electrostatic forces.

Acrylic Resins↗

Adsorption of drugs onto a poly(acrylic acid) grafted cation-exchange membrane.

The influence of pH, ionic strength and the concentration of albumin in the adsorption medium as well as the charge and lipophilicity of a model drug on their adsorption onto poly(acrylic acid) grafted poly(vinylidene fluoride) (PAA-PVDF) membranes was evaluated. The PAA-PVDF membrane is a responsive porous polymer membrane that we have studied for controlled drug delivery. Sodium salicylate (anionic), flunitrazepam (neutral), primidone (neutral), desipramine (cationic) and thioridazine (cationic) were used as model drugs. The extent of drug adsorption was dependent on pH. Drug adsorption was enhanced by the dissociation of the grafted PAA chains and by a positive charge and a high lipophilicity of the drug. Increasing the ionic strength of the medium retarded the adsorption of the cationic drugs. Interestingly, the present results showing that drugs are adsorbed onto the membrane while albumin is not adsorbed onto the membrane suggest that the PAA-PVDF membrane may be suitable for separating drugs from proteinaceous substances for subsequent monitoring and evaluation.

Acrylates↗

Transport of drugs across porous ion exchange membranes.

Porous ion exchange membranes have potential applications for drug delivery systems. Permeability of these membranes can be controlled by environmental factors like pH and ionic strength but also the drug properties have an important role in the permeation process. In this paper the influence of the drug charge, lipophilicity and molecular weight on the diffusional drug flux is demonstrated. The membranes under study were poly(acrylic acid) (PAA) grafted porous poly(vinylidene fluoride) (PVDF) membranes which are cation selective due to the partial ionization of carboxyl groups in grafted PAA chains. At low pH the membrane pores are open and the drugs can diffuse through the membrane quite easily. However, at pH 7 the grafted chains partially block the pores and the diffusional flux of bigger drug molecules (Mw9400) decreases five orders of magnitude and also the flux of smaller molecules is clearly reduced. When the influence of the drug charge on the diffusion of the drugs across the membranes was studied, it turned out that the PAA-PVDF membranes facilitate the transport of cationic drugs and repel anionic ones. The presented mathematical model, based on Donnan drugs equilibrium and measured transport number data, predicted the observed trends reasonably well.

Biological Transport↗

Estimation of the probabilities of 3D clusters in functional brain images.

The interpretation of functional brain images is often hampered by the presence of noise. This problem is most commonly solved by using a statistical method and only considering signals that are unlikely to occur by chance. The method used should be specific and sensitive, specific because only true signals are of interest and sensitive because this will enable more information to be extracted from each experiment. Here we present a modification of the cluster analysis proposed by Roland et al. (Human Brain Mapping 1: 3-19, 1993). A covariance model is used to test hypotheses for each voxel. The generated statistical images are searched for the largest clusters. From the same data set noise images are generated. For each of these noise images the autocorrelation function is estimated. These estimates are subsequently used to generate simulated noise images, from which a distribution of cluster sizes is derived. The derived distribution is used to estimate probabilities for the clusters detected in the statistical images generated by testing the hypothesis. This presented method is shown to be specific and is further compared with SPM96 and the nonparametric method of Holmes et al. (J. Cereb. Blood Flow Metab. 16: 7-22, 1996).

Artifacts↗

Bone volume in human temporomandibular autopsy joints with and without erosive changes.

The aim was to compare the trabecular bone volume (TBV) and the total bone volume (TOBV) of human temporomandibular joints (TMJ) with erosive changes with those of joints without erosive changes. We examined 35 TMJ autopsy specimens from 19 individuals aged 66 88 years. Sagittal sections of the joints were analyzed microscopically for erosive hard-tissue changes. The TBV and the TOBV of the sections were assessed with the aid of computerized image analysis. A significant increase in trabecular and total bone volume was found in condyles with erosive changes (TBV = 21%, TOBV = 54%) as compared with condyles without erosive changes (TBV = 15%, TOBV = 40%). The trabecular bone volume of the temporal component was also increased (TBV = 24%) in joints with erosive changes in the condyle as compared with joints with unaffected condyles (TBV = 16%). The findings indicate that the relative bone mass may play a role in the development of erosive changes in the TMJ.

Age Factors↗

Survival of orphans in 19th century Sweden--the importance of remarriages.

The study aims at elucidating the fate of orphans in 19th century Sweden. A cohort of all children born in the region of Sundsvall was followed. The Cox regression model was used. The population increased 12-fold in the sawmill parish, and doubled in the other parishes. Every 13th child lost either his or her mother or father. The death risk represented by being a motherless infant exceeded every other death risk for the child, and was further enhanced if parents were crofters or coming from the sawmill parish. For children beyond the age of 1 year, factors other than parental deprivation became decisive. Step-parents had an immense positive influence on the survival of the children. The social network worked relatively well for those children who were orphans beyond the age of 1 year. The motherless infants had the worst outcome. The best chance for survival was found for children with step-parents.

Age Factors↗

Concavity of the posterior surface of the temporomandibular condyle: clinical cases and autopsy correlation.

OBJECTIVES: To elucidate the significance of the radiographic finding of a concavity of the posterior surface of the temporomandibular condyle. METHODS: Three clinical cases with a concavity were followed up clinically and radiographically. A total of 39 temporomandibular joint (TMJ) autopsy specimens were examined by corrected sagittal tomography and seven condyles with a concavity of the posterior surface found. They were analysed microscopically together with three joints with a normal, rounded condyle. RESULTS: At follow-up tomography, two of the clinical cases revealed no change while the third patient had erosive changes after 7 months. The microscopic findings of the autopsy specimens varied. The articular cartilage in three of the seven joints with a concavity was similar to that in the normal condyles. The outer surface of the articular cartilage was sometimes uneven and the cartilage thickened, with an irregular junction between the articular cartilage and subchondral bone. In three joints the cartilage in the concavity had been replaced by granulation tissue. All seven joints had increased cellular activity in the concavity. CONCLUSIONS: The radiographic finding of a concavity in the posterior surface of the condyle is not specific. When small and well-defined it is indicative of remodelling and of osteoarthrosis when larger and with a diffuse outline.

Adult↗

Diclofenac sodium as an alternative treatment of temporomandibular joint pain.

In a double-blind study, diclofenac sodium (Voltaren), 50 mg two or three times a day, was compared with placebo in 32 patients with pain localized to the temporomandibular joint (TMJ). The patients were allocated into two equally large groups. A visual analog scale was used to estimate the pretreatment degree of pain. The treatment effect was assessed as the frequency of joint and muscle pain and by the patients' own evaluation of improvement. The change in the clinical condition was assessed by tenderness to palpation of the TMJ and masticatory muscles and by mandibular mobility. The frequency of TMJ pain showed a greater reduction in the diclofenac group than in the placebo group, and there was a significant reduction of daily TMJ pain in the diclofenac group. The diclofenac group also showed a significant decrease in tenderness to palpation of the masticatory muscles in comparison with the placebo group. The patients with short duration of pain showed the best response to diclofenac. There was no evidence in this study to prove that diclofenac should be used as a primary treatment of TMJ pain, but it could be used as a complement to other treatments of acute TMJ pain.

Adult↗

Clinical pharmacokinetics of amonafide (NSC 308847) in 62 patients.

Amonafide (A) demonstrates dose-related increases in area under the curve (AUC) and Cmax values. Total body clearance for A (ranging from 44.2 to 53.8 L/hr/m2) is relatively constant within the dosing range of this study. The dose-related increase of AUC was also observed for the two identified metabolites, acetylamonafide (AA) and noramonafide (NA). A and NA plasma data could be described by a four-compartmental model (two compartments for A, one compartment each for NA and AA). The fitting for NA was poor owing to its low plasma concentration. The terminal half-lives for A, NA, and AA were in the range of 3-6 hr. No cumulative accumulation of parent compound or metabolites was detected after daily administration, The concentrations of A, NA, and AA 24 hr after dosing were either below or very close to the quantitative limits of the assay. Polymorphic disposition of A was confirmed by a frequency distribution of AUC value versus dose plot.

Adenine↗

Temporomandibular joint disc position in arthrography. A descriptive analysis of the observer performance.

OBJECTIVES: To explore the relationship between the use of diagnostic cues and observer performance in the diagnosis of the temporomandibular joint (TMJ) disc position. METHODS: Thirty arthrographic examinations using fluoroscopy alone and combined with either transcranial radiography or tomography were selected. Seven observers assessed the examinations with the aid of reference images and written diagnostic cues for three disc diagnoses. After one month three of the observers repeated the assessments and noted how they applied the diagnostic cues. Later, they made a consensus report on how the cues were applied to each joint. RESULTS: The seven observers agreed unanimously with the reference diagnosis by fluoroscopy alone in 11 joints and in 14 when supplemented with transcranial radiography or tomography. Seven joints were given three different diagnoses by the seven observers when fluoroscopy was used alone and five when supplemented with transcranial radiography or tomography. The cues were applied with confidence in those joints where the observers were unanimous but in those with three different diagnoses, the anatomical features described in the cues were difficult to identify or the findings were ambiguous as they did not match the cues. CONCLUSIONS: It appears difficult to define radiographic cues applicable to all TMJ disc positions.

Arthrography↗

Corrected sagittal tomography of the temporomandibular joint. Influence of errors in film and patient positioning on linear and angular measurements.

The aim of this study was to assess the variation in film and patient positioning in horizontally corrected sagittal tomography of the temporomandibular joint (TMJ). The influence of this variation on linear and angular measurements of some anatomic structures of the TMJ was also studied. There was no significant variation in film positioning in the tomograph, using a multi-film cassette. The variation in positioning the patient in the tomograph was significant when four dental assistants were asked to place the Frankfort plane parallel to the horizontal plane. The measurements with the film in a straight position were compared with the measurements with the film angulated, to simulate the mean variation in film and patient positioning. Linear and angular measurements of anatomic structures were performed in arthrotomograms of 58 joints, representing joints with superior disk position and joints with anterior disk position with and without reduction. There was a difference between the two measurements for four different distances and one angle independent of diagnosis. No differences could be found between patients belonging to the different diagnostic groups. The results indicate that variation in patient positioning influences linear and angular measurements of anatomic structures in TMJ arthrotomograms.

Analysis of Variance↗

Microscopy and tomography of erosive changes in the temporomandibular joint. An autopsy study.

Thirty-nine temporomandibular joint autopsy specimens were examined by microscopy and tomography for erosive changes. We found two types of erosive changes, an extensive type with complete loss of cartilage and a local type with retained articular cartilage. On microscopic examination nearly twice as many temporal components as condyles were eroded. The erosions were generally more extensive in the condyle. Erosions in the condyle were evenly distributed. In the temporal component there was a slight predominance of erosions located to the lateral part of the tubercle. The radiologic investigation underestimated both the presence and the extent of the erosions. Positive predictive values and negative predictive values were 0.70 and 0.83, respectively, for erosions in the condyle and 0.91 and 0.68 for erosions in the temporal component. It is suggested that the initial event in osteoarthrosis of the TMJ can occur as a subarticular hard-tissue change. The need for more accurate diagnostic tools than radiography should be stressed.

Aged↗

Observer performance and diagnostic outcome in diagnosis of the disk position of the temporomandibular joint using arthrography.

Observer performance and diagnostic outcome in the diagnosis of the disk position of the temporomandibular joint by arthrography were investigated. Three different radiographic techniques were studied: fluoroscopy, fluoroscopy in combination with lateral transcranial radiography, and fluoroscopy in combination with corrected sagittal tomography. Seven observers were asked to assess 30 joints representing three diagnoses, namely superior disk position and anterior disk position with and without reduction. The intraobserver agreement was high for all three techniques. The interobserver agreement of the seven observers when the disk position was diagnosed by fluoroscopy in combination with lateral transcranial radiography (Kappa index 0.68) was higher than that with fluoroscopy alone (Kappa index 0.54) and that with fluoroscopy in combination with corrected sagittal tomography (Kappa index 0.56). The sensitivity, specificity, and predictive values of fluoroscopy in combination with lateral transcranial radiography were also higher than those of the other radiographic techniques. Judged from this study, the observer agreement and the diagnostic outcome for arthrography with the use of the three examined techniques are high when well-defined criteria and reference images are applied.

Adolescent↗

Therapy of refractory/relapsed acute myeloid leukemia and blast crisis of chronic myeloid leukemia with the combination of cytosine arabinoside, tetrahydrouridine, and carboplatin.

Eight patients, of whom four had acute myeloid leukemia (AML) and four had chronic myeloid leukemia (CML) blast crisis, were treated with a combination of cytosine arabinoside (ARA-C: 1,600 mg/m2 in three patients, 1,200 mg/m2 in five patients), tetrahydrouridine (THU: 2,800 mg/m2 in two patients, 2,646 mg/m2 in one patient, 2,100 mg/m2 in five patients), and carboplatin (900 mg/m2 in four patients, 720 mg/m2 in one patient, 450 mg/m2 in three patients). As a result of this treatment, five of the eight patients became aplastic. Two of the four patients with CML blast crisis reverted to the chronic phase and two of the four patients with acute nonlymphocytic leukemia (ANLL) attained a remission (one partial remission and one complete remission). The major toxicities included myelosuppression, unacceptable hepatotoxicity, and diarrhea. Pharmacokinetics studies revealed that the addition of carboplatin did not significantly change the disposition of ARA-C. ARA-C levels were not significantly changed in comparison with those obtained in a prior study of ARA-C with THU (ARA-C plasma levels at 3 h, 2630 +/- 1170 ng/ml).

Acute Disease↗