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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 397 records · Page 22Linked to original sources

Antibacterial peptides from pig intestine: isolation of a mammalian cecropin.

Pig small intestine was used as starting material for a batchwise isolation of a peptide fraction enriched in antibacterial activities against Escherichia coli (anti-Ec factor) and against Bacillus megaterium (anti-Bm factor). Separation and further purification were by different types of chromatography. Sequence analysis showed the anti-Bm factor to be apparently similar to vasoactive intestinal peptide. The anti-Ec factor was found to have a 31-residue sequence that was cecropin-like. It was named cecropin P1 and its structure was confirmed by solid-phase synthesis. Synthetic cecropin P1 with and without C-terminal amide was assayed on eight different bacteria. Mobility comparison between synthetic and natural cecropin P1 indicates that the natural peptide has a free C-terminal carboxyl group.

Amino Acid Sequence↗

The clinical efficacy of budesonide in hay fever treatment is dependent on topical nasal application.

During the last decade topical glucocorticoids have been established as the first hand choice for the treatment of allergic rhinitis. Although they are clinically effective, their precise mode of action has not been sufficiently clarified. In order to evaluate whether the clinical effect is dependent on the topical administration a randomized, double-blind, double-dummy study was performed. Ninety-eight patients with allergic rhinitis due to birch pollen were recruited at two centres in southern Sweden. The patients received one of the following three treatment alternatives: 200 micrograms of nasally applied budesonide twice daily, 250 micrograms of budesonide given orally twice daily or a placebo. The selection of the doses was based on previous pharmacokinetic studies giving almost equal plasma levels of the nasally and orally administered budesonide. To evaluate the possible clinical efficacy of the treatment, the patients kept a diary in order to register symptoms according to a 0-4 scale. After a run-in week with no treatment the patients entered the treatment period which lasted for 3 weeks. A total of 96 patients completed the study. The symptom data showed that topically applied budesonide was clinically effective with a pronounced reduction in all the nasal symptoms registered and compared with placebo treatment there was a statistically significant difference in favour of the budesonide treatment (P less than 0.001). The nasal symptoms of the patients receiving oral budesonide did not differ from those receiving placebo. Intranasally administered budesonide proved to be significantly more effective than orally applied budesonide (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Anti-idiotypic B-cell lines from a patient with monoclonal gammopathy of undetermined significance.

The B-cell repertoire in a patient with benign monoclonal gammopathy of unknown significance was studied using Epstein-Barr virus transformation of peripheral lymphocytes. The presence of anti-idiotypic B cells producing monoclonal antibodies that reacted with idiotypic determinants on the monoclonal immunoglobulin was verified. The two monoclonal anti-idiotypic antibodies studied were of the IgM-kappa type. Such anti-idiotypic antibodies may be part of an idiotypic network regulation of the monoclonal B-cell population.

Antibodies, Anti-Idiotypic↗

Eosinophils and eosinophil cationic protein in nasal lavages in allergen-induced hyperresponsiveness: effects of topical glucocorticosteroid treatment.

Airway challenges with allergen are frequently followed by an increase in responsiveness to both specific and unspecific stimuli. This phenomenon in the lower airways has been linked to the presence of a late phase response to allergen challenge. One of the hallmarks of the late phase response is a tissue infiltration of granulocytes, specifically the eosinophils. A hypothesis for the increase in responsiveness has been that local activation of these eosinophils with subsequent release of the toxic granular constituents leads to a decrease in the barrier function of the airway epithelium. The aim of the present study was to further explore this hypothesis. Ten patients with previously demonstrated nasal allergen-induced hyperresponsiveness participated in a double-blind cross-over study involving pretreatment for various periods with topical glucocorticosteroids. The patients were challenged intranasally with allergen on one day, rechallenge 24 h later and the increase in responsiveness noted. In a nasal lavage performed immediately prior to challenge the number of eosinophilic granulocytes and the level of eosinophilic cationic protein (ECP) was determined. As expected, the placebo-treated patients demonstrated an increase in nasal responsiveness at rechallenge accompanied by a tendency for an increase in eosinophils as well as ECP in the lavage preceding the rechallenge compared with the initial allergen challenge 24 h previously. The amount of ECP found in the lavage on the second day correlated with the TAME-esterase activity, a marker of ongoing inflammatory activity (r = 0.64; P less than 0.05) in the same lavage, suggesting participation of the eosinophilic granulocyte in the inflammatory response to allergen.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Disialotransferrin developmental deficiency syndrome.

Seven mentally deficient children and adolescents (three pairs of siblings and one singleton) were studied. A peculiar external appearance, a characteristic neurohepatosubcutaneous tissue impairment syndrome and, as a biological marker, an abnormal sialic acid transferrin pattern were characteristic features. All seven seemed odd from birth and prone to acute cerebral dysfunction during catabolic states. Abnormal lower neurone, cerebellar, and retinal functions dominated from later childhood. The disialotransferrin pattern found in serum and cerebrospinal fluid is thought to be the biological marker of a newly discovered inborn error of glycoprotein metabolism with autosomal recessive inheritance.

Adolescent↗

Objective monitoring of the allergic inflammatory response of the nasal mucosa in patients with hay fever during natural allergen exposure.

A method is presented for the objective monitoring of the inflammatory response of the nasal mucosa to natural allergen exposure through measurements of biochemical markers such as TAME-esterase activity in a daily nasal lavage. Nine patients with strictly seasonal allergic rhinitis caused by birch pollen and five healthy nonatopic control subjects participated in the present study, which started 1 wk before the birch pollen season and continued throughout the entire pollen season. A diary card was used to assess daily nasal symptoms, and a daily nasal lavage was performed once every afternoon. The degree of pollen exposure was assessed by daily pollen counts. The TAME-esterase activity in the lavage fluid from the allergic patients, but not in that from the nonallergic control subjects, increased significantly during pollen exposure despite low pollen counts and was found to correlate with daily nasal symptoms (r = 0.36; p less than 0.05) and the degree of pollen exposure (r = 0.45; p less than 0.01). The area under the curve for the daily TAME-esterase measurements thus differed significantly (p less than 0.02) between allergic patients (158 +/- 28) and control subjects (74 +/- 9). This approach for the monitoring of patients with hay fever during natural allergen exposure will make further objective studies on the pathophysiology and pharmacology of hay fever possible. We also provide support for the validity of previous findings obtained in allergen challenge situations utilizing the lavage approach.

Adult↗

Clinical results with titanium crowns fabricated with machine duplication and spark erosion.

A new method for fabrication of metal crowns has been developed by one of the authors (M.A.). There are two principles involved: machine duplication of models and electric discharge machining. The metal used is pure unalloyed titanium, which is processed as a coping and later covered by a composite resin. In 1986, 205 separate titanium crowns were made on 149 patients. One year later 192 crowns on 137 patients could be examined. Five crowns had been replaced by new ones owing to fracture of the composite resin. In accordance with the CDA quality evaluation system the following results were obtained for the remaining 187 crowns: margin integrity, 186 excellent or satisfactory (99.5%); anatomic form, 185 excellent or satisfactory (98.9%); and surface and color, 181 excellent or satisfactory results (96.8%). The 1-year results are promising, and further follow-up studies will be made.

Acrylic Resins↗

Pharmacokinetics and central haemodynamic effects of doxorubicin and 4'epi-doxorubicin in the pig.

The relationship between the cardiotoxicity and the haemodynamics/pharmacokinetics of clinical concentrations of doxorubicin and 4'epi-doxorubicin was studied. Twelve pigs were randomized to receive i.v. infusions of either drug of 50 mg/m2 over 3.0 min. Aortic, pulmonary arterial, coronary sinus and central venous plasma concentrations of the agents were determined until 180 min after the infusion. The V5 ECG, left ventricular dP/dT, aortic, pulmonary arterial and right atrial pressures were recorded continuously, cardiac output and coronary sinus blood flow were recorded intermittently. No haemodynamic changes were recorded after administration of either drug. Pharmacokinetic data indicated myocardial extraction, followed by myocardial release of both drugs. This release was higher after administration of 4'epi-doxorubicin than after doxorubicin, within the range 2-4 min and 20-40 min after the infusion. The tendency of greater myocardial release of 4'epi-doxorubicin may explain its lower cardiotoxicity.

Animals↗

Pharmacokinetics of intra-arterial mitomycin C with or without degradable starch microspheres (DSM) in the treatment of non-resectable liver cancer.

The effects of degradable starch microspheres (DSM) on mitomycin C pharmacokinetics and bone marrow toxicity were studied in a phase II multicenter study. Sixty-three patients with non-resectable primary or secondary liver cancer were randomized to receive either i.a. mitomycin C 15 mg/m2 first, followed 5 weeks later by mitomycin C 15 mg/m2 plus DSM 360 mg administered into the hepatic artery (group I) or the same treatments in the opposite sequence (group II). In 36 out of 47 patients who received at least 2 treatments, peripheral venous blood samples were analyzed for mitomycin C pharmacokinetics on a minimum of 2 paired courses. In all patients, the area under the concentration time curve (AUC) was significantly lower when the drug was co-administrated with DSM, but the terminal half-life (t1/2) of mitomycin C was unchanged. In group I the addition of DSM resulted in a significantly lowered AUC, but not in group II. The discrepancy between the 2 groups is probably due to differences in DSM-induced intra-hepatic shunting. The addition of DSM resulted in significantly higher platelet nadir values, but unchanged white blood cell count nadir value. In conclusion, DSM reduce the systemic exposure of mitomycin C and seem to lessen the haematologic toxicity judged from a less pronounced decrease in platelets.

Adult↗

Institutionalization of the elderly and characteristics of nursing home patients.

To characterize nursing home patients and to study the prevalence of institutionalization 191 patients living in four somatic nursing homes in western Sweden were investigated. Of the total population over 65 years 7.8% were institutionalized, 2.6% in somatic nursing homes. The need for care increased markedly after 80 years of age. Most commonly (45%), the patients were admitted from emergency somatic wards. The mean age was 82.5 years, 74% were single and 60% were women. The mean period of care was 1.82 years. 87% had more than one diagnosis. The most common diseases concerned the circulatory system (51%) and the musculoskeletal system (43%). Dementia was diagnosed in 41% at admittance, but functional tests revealed a much higher frequency (72%). Conclusions. The nursing home patient was very old, was mostly single and had multiple diseases. The prevalence of dementia was high.

Age Factors↗

The home care patient. A comparison with the nursing home patient.

Forty-two patients receiving medical home care (MHC) were studied and compared with a group of 191 nursing home (NH) patients in the same area. Most MHC patients were over 65 years old. In both groups the illnesses that dominated were mainly circulatory and musculoskeletal diseases. The NH patients had significantly lower test results concerning intellectual, motor and ADL functions. The frequency of dementia was 3 times higher for both MHC and NH patients than for the average population in the same age groups. Depressed mood, anxiety, fear and panic were common symptoms for MHC as well as for NH patients. Both groups of patients investigated had frequent communication with relatives and friends. MHC patients took part in activities outside the home less frequently than NH patients. The results of this study indicate that MHC and NH patients constitute two different groups, that both NH and MHC care are needed, and that one form cannot replace the other. The high frequency of dementia in both groups stresses the point that mental impairment is a strong factor for the need of care.

Activities of Daily Living↗

Drugs prescribed for elderly patients in nursing homes or under medical home care.

The consumption of drugs was registered for 191 nursing home patients (NH, median age 84) and for 42 medical home care patients (MHC, median age 74). Drug treatment was common in both groups and somewhat higher in MHC (4.4 and 4.9 drugs, respectively per patient). The proportion of men/women on drugs and the average number of drugs prescribed differed between the sexes only exceptionally. Drugs for cardiovascular diseases, psychotropic drugs, laxatives and analgesics were the most frequently used. Although psychotropic drugs were frequently prescribed, symptoms of emotional disturbances appeared undertreated. Demented patients received anxiolytic drugs less frequently than non-demented. The NH group received inadequate pain relief, there were few prescriptions for infectious diseases, and intravenous infusions were rare.

Aged↗

Isolation and characterization of porcine diazepam-binding inhibitor, a polypeptide not only of cerebral occurrence but also common in intestinal tissues and with effects on regulation of insulin release.

The polypeptide DBI (diazepam-binding inhibitor) has been purified from the porcine upper intestine, where it is abundant. Porcine mature DBI is composed of 86 amino acid residues and has a blocked N-terminus. The primary structure, the first DBI structure determined at the protein level, differs from those indirectly deduced for human and rat DBI at 11 and 17 positions, respectively. In total, the three mammalian DBIs differ at 22 positions but have exactly identical C-terminal 11-residue segments, highly charged and ending with C-terminal isoleucine. The porcine DBI inhibits both the early and the late phase of glucose-induced insulin release from the isolated perfused rat pancreas. Thus, the results identify by direct analysis the presence of DBI at a non-cerebral localization (gut), establish a novel structural form (porcine) and demonstrate a novel bioactivity (on insulin release). These aspects are of special interest in relation to the conserved segments, including the one at the C-terminal end, which may constitute functionally important parts of the polypeptide. It is possible that DBI belongs to a new family of gut polypeptides which inhibit glucose-mediated insulin release by hormonal and/or neurocrine mechanisms.

Amino Acid Sequence↗

Cardiopulmonary hemodynamics and pharmacokinetics after hepatic intraarterial infusion of 5-fluorouracil (5-FU). An experimental study in the pig.

Reported 5-FU-induced cardiac side effects may be explained by drug-induced hemodynamic changes and/or by direct myocardial toxicity due to regional drug uptake. This question was studied in 11 animals given constant infusions and 6 animals given bolus 5-FU infusions into the hepatic artery. Six animals, which received normal saline infusion, served as controls. A second aim was to study possible pulmonary drug clearance. Aortic, pulmonary arterial, and coronary sinus plasma 5-FU concentrations were determined during constant and after the bolus infusions of 5-FU. The V5 ECG, aortic, pulmonary arterial, and right atrial pressures were recorded continuously, and cardiac output and coronary sinus blood flow were recorded intermittently in all animals. No significant alterations in hemodynamic variables were seen during constant infusion. After the bolus infusion, an increased arterio-mixed venous oxygen content difference was recorded. Pharmacokinetic data after 3-min infusions indicated pulmonary drug uptake and release; during constant infusions, the data indicated myocardial drug uptake. As there were no alterations in myocardial oxygen demand or supply or in systemic hemodynamics during this myocardial drug uptake, it is likely that the cardiotoxicity is related to the direct effects of the drug on cardiac myocytes.

Animals↗

Y;autosome translocations and mosaicism in the aetiology of 45,X maleness: assignment of fertility factor to distal Yq11.

Three 45,X males have been studied with Y-DNA probes by Southern blotting and in situ hybridization. Southern blotting studies with a panel of mapped Y-DNA probes showed that in all three individuals contiguous portions of the Y chromosome including all of the short arm, the centromere, and part of the euchromatic portion of the long arm were present. The breakpoint was different in each case. The individual with the largest portion (intervals 1-6) is a fertile male belonging to a family in which the translocation is inherited in four generations. The second adult patient, who has intervals 1-5, is an azoospermic, sterile male. These phenotypic findings suggest the existence of a gene involved in spermatogenesis in interval 6 in distal Yq11. The third case, a boy with penoscrotal hypospadias, has intervals 1-4B. In situ hybridization with the pseudoautosomal probe pDP230 and the Y chromosome specific probe pDP105 showed that Y-derived DNA was translocated onto the short arm of a chromosome 15, 14, and 14, respectively. One of the patients was a mosaic for the 14p+ translocation chromosome. Our data and those reported by others suggest the following conclusions based on molecular studies in eight 45,X males: The predominant aetiological factor is Y;autosome translocation observed in seven of the eight cases. As the remaining case was a low-grade mosaic involving a normal Y chromosome, the maleness in all cases was due to the effect of the testis determining factor, TDF. There is preferential involvement of the short arm of an acrocentric chromosome (five out of seven translocations) but other autosomal regions can also be involved. The reason why one of the derivative translocation chromosomes becomes lost may be that it has no centromere.

Adolescent↗

Characterization of a (Y;4) translocation by DNA hybridization.

A phenotypically normal male with azoospermia was found to have a translocation between the short arm of the Y chromosome and the distal long arm of a chromosome 4. By cytogenetic analysis it could not be determined whether the translocation was reciprocal, nor whether it was balanced. In situ DNA hybridization with two pseudoautosomal and one Y-specific probe demonstrated that the breakpoint was on distal Yp and that there was Y chromosome material on 4q. Thus the translocation was reciprocal and could be characterized as t(Y;4)(pll;q32). There was no evidence for loss of Y-DNA sequences as judged by Southern blotting with Y-DNA probes. Thus the translocation may be balanced. We conclude that DNA hybridization can be used to refine considerably the cytogenetic analysis of such translocations.

Adult↗

The effect of platelet activating factor on nasal hypersensitivity.

Platelet activating factor (PAF) is known to have a wide range of biological activities. In the lower airways PAF has been suggested as the biochemical mediator partly responsible for the bronchial hyperreactivity which is a feature of asthma. In order to study whether PAF has a similar effect in the upper airways, we carried out a double blind, placebo-controlled cross-over study in twelve patients with strictly seasonal allergic rhinitis. The study was performed in pollen-free winter months. 26 micrograms PAF or placebo was sprayed into each nasal cavity 8 h and 1 h before a nasal allergen challenge. The nasal response to PAF and the allergen challenge that followed was monitored by repeated measurements of nasal expiratory peak flow rate and symptom scores. PAF induced only minor changes in nasal patency and nasal symptoms as compared to placebo. However, pretreatment with PAF induced an increase in responsiveness of the nasal vasculature to the allergen challenge that followed. This was registered as a small, but statistically significant increase in the symptom scores for nasal blockage, from 1.7 (0.3; SEM) after placebo pretreatment to 2.4 (0.36; SEM) after PAF (p less than 0.05). A similar trend was also noted for the measurements of nasal peak flow. The other response parameters, sneezes and secretion, remained identical. These results suggest that PAF may play a role in human nasal hyperreactivity, but it appears that PAF is not a major mediator involved in the induction of this phenomenon.

Administration, Inhalation↗