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Biomedical subjects

S Jacobsson

Publications and source records attributed to S Jacobsson.

At least 37 records · Page 2Linked to original sources

Flow cytometric analysis of megakaryocyte ploidy in chronic myeloproliferative disorders and reactive thrombocytosis.

Megakaryocyte (MK) ploidy patterns were analysed by flow cytometry in 29 newly diagnosed and previously untreated patients with chronic myeloproliferative disorders (MPD) and concomitant thrombocytosis, in 9 patients with reactive thrombocytosis (RT) and in 12 healthy individuals. Unfractionated bone marrow from routine aspirates was used. MKs were identified with a fluorescein labelled monoclonal antibody specific for glycoprotein IIIa (GPIIIa) and DNA was stained with propidium iodide. For the 12 healthy volunteers the mean modal ploidy number was 16 N; the 9 patients with RT displayed an identical MK ploidy pattern. The frequency of MKs with a ploidy > or = 32 N was 45% among the patients with essential thrombocythaemia (ET) compared to 32% among the healthy volunteers (p < 0.001). MKs with ploidy number > or = 64 N, comprising approximately 13% of the total number of MKs, was a characteristic finding in the patients with ET. Similar findings were present in 8 patients with polycythaemia vera (PV). In patients with PV 34% and 6% of the MKs displayed ploidies > or = 32 N and > or = 64 N, respectively. In contrast, a distinct shift towards lower ploidy number, with 63% of MKs < or = 8 N, was found among the 4 patients with chronic myeloid leukaemia (CML). The present results indicate that by using flow cytometric analysis of MK ploidy distribution in patients with thrombocytosis, those with a reactive cause are likely to be discriminated from patients with myeloproliferative thrombocytosis, i.e. PV and ET on one hand and CML on the other hand. The distinction between ET and PV, however, has to be made on other grounds.

Adult↗

The platelet-specific alloantigen PlA1 (HPA-1a): a comparison of flow cytometric immunophenotyping and genotyping using polymerase chain reaction and restriction fragment length polymorphism in a Swedish blood donor population.

BACKGROUND: There is an increasing interest in the development of rapid and reliable techniques for platelet alloantigen typing. STUDY DESIGN AND METHODS: By use of standardized flow cytometry and a specific human alloantiserum, 236 Swedish blood donors were immunophenotyped for the platelet-specific alloantigen, PlA1 (HPA-1a). RESULTS: Ten individuals (4.2%) had low fluorescence intensities and were considered PlA1-negative (HPA-1a-negative); all of them also demonstrated a PlA2/PlA2 (HPA-1b/1b) genotype in a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay of the underlying DNA polymorphism. The remaining population had clear positive fluorescence and was regarded as PlA1-positive (HPA-1a-positive). The fluorescence distribution histogram among PlA1-positive (HPA-1a-positive) individuals was dome-shaped, and those individuals who were homozygous for PlA1 (HPA-1a) could not be distinguished from those who were heterozygous. This finding was further substantiated by PCR-RFLP analysis of the PlA1/PlA2 (HPA-1a/1b) genotype; a heterozygous genotype was found among those having a medium fluorescence intensity as well as among those having a strong fluorescence intensity. CONCLUSION: Flow cytometry is a valuable tool for large-scale detection of PlA1 (HPA-1a). However, flow cytometry based on only one antiserum cannot distinguish between homozygous and heterozygous carriers of PlA1 (HPA-1a). For zygosity testing and when platelets are difficult to obtain, the PCR-RFLP technique is the assay of choice.

Antigens, Human Platelet↗

Evidence for a light chain restriction of glycoprotein Ib/IX and IIb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura (ITP).

To address the assumption of clonally restricted antibodies in immune thrombocytopenias we studied sera from 19 patients with chronic ITP known to possess antibodies reactive with glycoprotein (GP) Ib/IX and/or GPIIb/IIIa. These sera were re-analysed using the standard monoclonal antibody immobilization of platelet antigens (MAIPA) assay and 16 patients exhibited IgG antibodies reactive with GPIIb/IIIa; seven patients showed also a reactivity with GPIb/IX. Employing a light-chain-specific MAIPA assay, 75% (12/16) of these sera displayed GPIIb/IIIa-specific antibodies that were light chain restricted; only 13% (2/16) of the GPIIb/IIIa reactive sera showed a mixed kappa and lambda phenotype. A light-chain-restricted phenotype was also seen for the GPIb/IX reactive antibodies. To further substantiate these findings, the MAIPA assay was modified in order to avoid interference from human anti-mouse antibodies. A high frequency of light-chain restricted platelet antibodies was also found using the modified MAIPA technique. These results support the hypothesis of a clonal B-cell expansion in immune thrombocytopenias, producing antibodies with a restricted idiotype repertoire and reacting with a limited number of epitopes.

Adult↗

Peripheral and intrasplenic platelet kinetics and bone marrow megakaryopoiesis in alpha-2b-interferon treated hairy cell leukemia.

In eight patients with previously untreated hairy cell leukemia (HCL), by using 111In-labelled platelets and megakaryocyte quantitation, the splenic platelet pooling and the platelet production rate (P) were evaluated before and during alpha-2b-interferon (IFN) treatment. Both before and after 8 months of IFN therapy the spleen was shown to pool a sizeable amount of the total body platelet mass. The average splenic platelet pools, prior to and after 8 months of IFN, were 58 +/- 17 and 47 +/- 11%, respectively. At the time when treatment was initiated, the patients were heterogeneous as regards the spleen size, platelet kinetics, and the bone marrow morphology. Three patients had values for P below the 95th percentile for a group of healthy control subjects; following IFN therapy they displayed a substantial increase in P. In three other HCL patients, with the largest spleens, the pre-treatment P was normal, or slightly above the values seen for the control subjects. In these patients, changes in splenic platelet pool size, blood volume, and platelet mean life-span accounted for the increase in platelet count observed in response to IFN. The mean megakaryocyte number and volume per microliter bone marrow increased during IFN therapy, while the mean P remained slightly reduced. It is concluded that splenic platelet pooling would explain the previously described difference in platelet counts between splenectomized and non-splenectomized patients treated with IFN.

Adult↗

Myotonic dystrophy revealed at videoradiography of deglutition and speech in adult patients with velopharyngeal insufficiency: presentation of four cases.

Patients with velopharyngeal insufficiency (VPI) without cleft palate, who appear for the first time in adulthood for treatment, will probably reveal a high percentage of undiagnosed myotonic dystrophy (MD). Videoradiography of deglutition and speech reveals the diagnosis. Eleven adult noncleft palate patients with VPI were studied with videoradiography of the pharynx and esophagus. Three exhibited functional radiographic manifestations of MD during deglutition and speech. The diagnosis confirmed by neurologic examination was not known or suspected prior to videoradiography. An additional patient with VPI and suspected MD displayed the same constellation of radiographic findings. Follow-up examinations confirmed the diagnosis of MD. Three of the four patients had had symptoms of VPI since childhood, but none had complaints of deglutition problems except for accidental nasal regurgitations.

Adult↗

Evaluation of amoxicillin clavulanate twice daily versus thrice daily in the treatment of otitis media in children. Danish-Swedish Study Group.

A total of 311 children who had recurrent otitis media or who had experienced failure of initial treatment of acute otitis media with phenoxymethylpenicillin, amoxicillin, ampicillin esters or cefaclor were entered into a single-blind study in two parallel groups in order to compare the clinical efficacy and safety of amoxicillin/clavulanate suspension given b.i.d. or t.i.d. for seven days. The patients were examined prior to the start of treatment, at an early follow-up visit 9 to 12 days after the start of treatment and at a late follow-up visit about three weeks later. Specimens for bacteriological culture were taken from the nasopharynx at entry, at the early follow-up visit, and at the late follow-up visit if there were symptoms of otitis. Both treatment groups showed a similar response, 90% or more of the patients being cured or showing improvement at the time of the early follow-up visit. The initial nasopharyngeal cultures showed growth of Haemophilus influenzae in 53% of the patients, Moraxella catarrhalis in 43% and Streptococcus pneumoniae in 39%. After treatment, cultures showed elimination of the initial pathogens in 30% of patients in both groups and recolonization in 23% in both groups. Haemophilus influenzae was the bacteria most frequently found in the nasopharynx at the first follow-up visit. Adverse effects, which consisted mostly of gastrointestinal and dermatological reactions, tended to be more common in the b.i.d. group but the difference was not statistically significant.

Acute Disease↗

Fibrin sealant in prevention of flexor tendon adhesions: an experimental study in the rabbit.

The effect of fibrin sealant on the development of adhesions in flexor tendon surgery was studied in both immobilized and active weight-bearing paws of rabbits. A partial laceration was produced and was treated with sutures alone or with both sutures and glue. Immobilized tendons treated in these ways showed no difference in adhesion formation, but in mobile tendons there was a difference at 6 weeks in gross appearance, scanning electron micrographic appearance, and strength of adhesions as measured when the distally cut tendon was pulled out of its sheath. These observations indicate that, after repair, a mobile flexor tendon heals with a smooth gliding surface and without formation of restricting adhesions when treated with fibrin glue around the suture site.

Animals↗

Geographical variation and time trends in the attack rate of coronary heart disease in five Swedish cities.

Based upon community myocardial infarction (MI) records in five Swedish cities, geographical variation and time trends in the attack rate of fatal and non-fatal MI have been evaluated. During the study period 1975-1982, a total of 7699 events were registered among men and 1823 events among women. The mean annual mortality was highest in the north, and a declining gradient in mortality was observed from the northern to the southern part of the country. The out-of-hospital death rate was highest in the north, while no difference in in-hospital mortality was observed. However, the geographical variation in the morbidity of MI was less consistent. Changes over time generally followed the same pattern in all cities. The attack rate of fatal and non-fatal MI tended to decline among women and men aged 60-64 years. The pattern was less consistent among younger men. Among women aged 50-59 years the mortality remained unchanged, but the attack rate of non-fatal MI increased in all cities. This increase was not explained by inclusion of less severe infarctions. A considerable proportion, about 85%, were recorded as primary events, emphasizing the possible role of primary prevention in obtaining a decrease in the incidence of the disease. The results of this study support previous findings of an important regional difference in the mortality of MI in Sweden. However, the magnitude of the regional variation in the incidence of coronary heart disease might be overestimated if only the mortality pattern is studied.

Adult↗

The effect of alpha-interferon on bone marrow megakaryocytes and platelet production rate in essential thrombocythemia.

In 10 patients with previously untreated essential thrombocythemia (ET), by using 111In-labeled platelets and megakaryocyte morphometry, the relation between platelet production rate and bone marrow megakaryocytes was evaluated before and during alpha-2b-interferon (IFN) therapy. A highly significant decrease in platelet count occurred during IFN therapy; the platelet counts, at baseline and after 2 and 6 months of IFN therapy, were 1,102 +/- 345 x 10(9)/L, 524 +/- 169 x 10(9)/L (P less than .0001), and 476 +/- 139 x 10(9)/L (P less than .0001), respectively. The decrement in platelet count was mainly a result of diminished platelet production rate, which at baseline and after 2 and 6 months of IFN therapy was 89 +/- 30 x 10(10) platelets/d, 53 +/- 18 x 10(10) platelets/d (P = .0033), and 45 +/- 20 x 10(10) platelets/d (P less than .0001), respectively. Also, a slight shortening of platelet mean life-span (MLS) was observed in response to IFN treatment; platelet MLS was 7.96 +/- 0.69 days at baseline and 6.68 +/- 1.30 days (P = .012) after 6 months of IFN therapy. IFN induced a significant decrease in bone marrow megakaryocyte volume; both megakaryocyte nuclear and cytoplasmatic volumes were affected. The mean megakaryocyte volume was 372 +/- 126 x 10(2) pL/microL at baseline and 278 +/- 147 x 10(2) pL/microL (P = .049) after 6 months of IFN therapy. However, the number of megakaryocytes did not show any significant change in response to IFN. It is concluded that alpha-IFN reduces platelet production rate and the peripheral platelet count in ET mainly through an anti-proliferative action on the megakaryocytes and to a considerably lesser degree by a shortening of platelet MLS.

Adult↗

Clinical efficacy of budesonide in the treatment of eczematous external otitis.

Sixty patients with mild to moderate forms of eczematous otitis externa were treated with budesonide and placebo in a double-blind controlled study using parallel groups. Each treatment period was preceded by otomicroscopic examination and thorough cleaning of the ear canal. The symptoms and signs were assessed with a score system ranging from 0 (no symptoms/signs) to 3 (severe symptoms/signs). Budesonide treatment was associated with a reduction in severity of all symptoms recorded and a marked improvement in erythema, swelling and discharge. Mechanical cleaning of the ear canal and placebo was not a sufficient treatment for this group of patients.

Administration, Topical↗

Distribution of penicillin-G and spiramycin to tissue cages and subcutaneous tissue fluid in calves.

Antibacterial drug concentrations in serum, tissue cage fluid (TCF) and subcutaneous tissue fluid (SF), sampled either by filter paper discs or by microcapillaries, were measured after single intramuscular injections of potassium penicillin-G (KPG), procaine penicillin-G (PPG) and spiramycin adipate in calves. Concentration-time curves had essentially similar profiles in serum and SF, but peak levels were lower and occurred later in SF. From approximately four hours after drug administration, penicillin-G levels in SF were similar to levels in serum after KPG as well as after PPG administration. Elimination half-life (t1/2) of penicillin-G in serum was similar to t1/2 in SF after PPG administration but was longer in SF than in serum after KPG administration. Spiramycin concentrations were higher in SF than in serum and the t1/2 of spiramycin in SF was longer than in serum. For all three drugs, the t1/2 was longer in TCF than in serum and concentration-time curves in TCF were characterised by a slow rise and decline. The two methods of sampling SF, by filter paper discs and by microcapillaries, gave similar but not identical results. Penetration into SF and TCF, measured as the total area under curve ratio, was better for spiramycin than for penicillin-G, but the latter drug had a higher penetration ratio to TCF in the first 12 hours.

Animals↗

Identification of cases of myocardial infarction: hospital discharge data and mortality data compared to myocardial infarction community registers.

Identification of incident myocardial infarction (MI) cases in a defined population using hospital discharge data and mortality data in combination has been suggested. This method of case identification was compared to that of use of MI community registers set up in accordance with principles adopted in a World Health Organization collaborative programme. The comparison comprised data for four Swedish cities over a number of years. On average 81% of incident hospital-treated cases below 65 years of age identified through MI community registers were found by the retrospective use of the method based on hospital discharge data and mortality data. Of hospital-treated cases identified by the latter method, 83% were also found by the MI community registers. For cases fulfilling the diagnostic criteria employed by the MI community registers this proportion would be higher, probably 87%-92%. Several reasons for cases being missed by either method were suggested by the results. According to the findings of this study, the case identification of the method based on hospital discharge data and mortality data seems to be somewhat less efficient compared to use of MI community registers. This may be of importance in descriptive epidemiological studies, but is of less significance in analytical studies. The relative efficiency of the former method could be improved by a more reliable system for the recording of hospital discharges. If supplemented by a validation procedure, it could yield sufficiently accurate data for many epidemiological applications at a fairly low cost.

Acute Disease↗

Cardiovascular risk factors in primary hyperparathyroidism: a 15-year follow-up of operated and unoperated cases.

The need for treatment of mild and apparently asymptomatic primary hyperparathyroidism (HPT) is questioned, but a raised incidence of cardiovascular disease has been regarded as evidence in favour of surgery. While it is well known that several risk factors for cardiovascular disease (hypertension, hyperlipidaemia and diabetes mellitus/impaired glucose tolerance) are overrepresented in HPT, it is not known whether surgery provides long-term normalization in these respects and reduces the risk of premature death. In a 15-year follow-up of a cohort of 172 subjects in whom mild hypercalcaemia was initially detected during a health screening, it was found that 56 subjects had died. 17 individuals had been operated on for HPT, 47 individuals were persistently hypercalcaemic, while 45 subjects had serum calcium within the normal range (seven individuals were lost to follow-up). There had been no significant differences in blood pressure between these groups of mildly hypercalcaemic patients and age- and sex-matched controls at the initial screening, but at follow-up blood pressure was significantly higher not only in subjects with persistent hypercalcaemia, but also in those who had been successfully operated on for HPT. Neither of the hypercalcaemic groups showed any significant deviations from the controls with regard to indices of lipid or glucose metabolism. These findings suggest that there is no simple cause-and-effect relationship to account for the propensity toward high blood pressure in primary HPT. Consequently it cannot be assumed that surgery for HPT will eliminate the increased risk of cardiovascular disease in patients with mild HPT.

Cardiovascular Diseases↗

ADP-induced platelet aggregation as a function of age in healthy humans.

In 120 healthy humans (58 males and 62 females) possible differences in platelet aggregability were investigated with respect to age and sex. By using a narrow range of final ADP concentrations (0.2-1.0 microM) primary and secondary aggregation were evaluated. The rate of primary aggregation was shown to be significantly related to increasing age and this was true for both sexes. As regards secondary aggregation the same pattern was seen in the group of male subjects. Thus, among the youngest (less than 34 years) the frequency of secondary waves was only one third of that encountered among the oldest (greater than 50 years). No similar association was detectable among the female subjects. The present study calls attention to some important issues which should be considered in platelet aggregation studies; the interpretation of data obtained from such studies invariably requires a careful selection of appropriate age- as well as sex-matched control groups.

Adenosine Diphosphate↗

[The effect of passive plates on the arrangement of the alveolar arch segments in unilateral total cheilognathopalatoschisis].

Maxillary alveolar arch morphology was studied from birth to palate repair at the age of 19 months in 24 children with complete unilateral cleft lip and palate (UCLP) treated with passive orthopaedic plates (treated children). 18 children with the same defect, who received no orthopaedic treatment, served as controls. The surgical procedures and the age at lip and palate repair were similar. Maxillary alveolar arch morphology was described by 15 linear and five angular measurements. No significant difference was found in total alveolar crest length neither between the cleft and the non-cleft maxillae nor between the treated children and the controls. Anterior alveolar arch width was significantly larger in the treated children at lip repair and at palate repair. Posterior alveolar arch width was significantly larger in the treated children at lip repair only. There was no significant difference in alveolar cleft width between the treated children and the controls at lip or at palate repair. Palatal cleft width decreased significantly in the treated children only. Medial rotation of both the cleft and the non-cleft maxillae was observed in both groups. The main difference was the absence of arch collapse in the treated children. At palate repair the relationship between the two maxillae was more favourable in the treated children for the development of the occlusion. The occlusion of the mixed dentition will be subject of a subsequent follow-up.

Cleft Lip↗