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Biomedical subjects

B Lind

Publications and source records attributed to B Lind.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease--12-month follow-up: angiogenic gene therapy.

OBJECTIVE: To test the safety and bioactivity of phVEGF-A165 after intramyocardial injection during 12-month follow-up. DESIGN: Open-labelled study. SUBJECTS: Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III-IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included. INTERVENTION: Via a mini-thoracotomy under general anaesthesia. phVEGF-A165 was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle. RESULTS: Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P < 0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.3+/-0.2 to 1.9+/-0.3 (P < 0.01) and nitroglycerine intake decreased from 39+/-15 to 12+/-5 tablets week(-1) (P < 0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A165 injection region was documented in all patients (P < 0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography. CONCLUSION: Intramyocardial injection of phVEGF-A165 is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial.

Aged↗
PubMed2001

Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A165 plasmid in patients with inoperable angina pectoris.

BACKGROUND: Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A165 via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. OBJECTIVE: To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A165 via thoracotomy. DESIGN: Open label, phase I/II. METHODS: Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional class III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer. RESULTS: Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients. CONCLUSIONS: Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A165 intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.

Aged↗
PubMed2001

Characterization and structural impact of five novel PROS1 mutations in eleven protein S-deficient families.

Heterozygozity for four novel missense mutations (W108C, W342R. E349K and L485S) and one novel 4 bp deletion (ACdelAAAG affecting codons 632-633) was identified in PROS1 of unrelated thrombosis prone Danish families with protein S type I or III deficiency. The 4 bp deletion results in a frameshift leading to replacement of the coding sequence for the 3 C-terminal amino acids by an abnormal extended sequence that codes for 9 amino acids. The E349K substitution was found in 7 families. Haplotype analysis using 7 microsatellite markers flanking PROS1 was consistent with a common founder for this mutation. The mutations reported here are most likely the cause of the protein S deficiency. Firstly, the four missense mutations cosegregate with the abnormal plasma protein S phenotype and lead to the loss of highly conserved amino acids. Secondly, computer analysis of structural models of protein S predicts that the substitutions could affect proper protein folding and/or stability. Analysis of platelet mRNA from subjects with the W108C, E349K, L485S mutation or the 4 bp deletion showed that mutated mRNA was expressed in significant amounts suggesting that mutated molecules are synthesized. Our results are compatible with defective protein folding/unstable molecules, impaired secretion and intracellular degradation of mutated protein, which appear to be the major molecular disease mechanisms for missense mutations and certain other mutations found in genetic disorders.

Adolescent↗
PubMed2000

Longitudinal study of methylmercury and inorganic mercury in blood and urine of pregnant and lactating women, as well as in umbilical cord blood.

We have investigated exposure to methylmercury (MeHg) and mercury vapor (Hg0) in pregnant women and their newborns in Stockholm. The women were followed for 15 months post delivery. MeHg, inorganic Hg (I-Hg), and total Hg (T-Hg) in maternal and cord blood were determined by automated alkaline solubilization/reduction and cold vapor atomic fluorescence spectrometry. T-Hg in urine was determined by inductively coupled plasma mass spectrometry. About 72% of the Hg in blood (n = 148) in early pregnancy was MeHg (median 0.94 microg/L, maximum 6.8 microg/L). Blood MeHg decreased during pregnancy, partly due to decreased intake of fish in accordance with recommendations to not eat certain predatory fish during pregnancy. Cord blood MeHg (median 1.4 microg/L, maximum 4.8 microg/L) was almost twice that in maternal blood in late pregnancy and was probably influenced by maternal MeHg exposure earlier and before pregnancy. Blood I-Hg (median 0.37 microg/L, maximum 4.2 microg/L) and urine T-Hg (median 1.6 microg/L, maximum 12 microg/L) in early pregnancy were highly correlated, and both were associated with the number of amalgam fillings. The concentrations decreased during lactation, probably due to excretion in milk. Cord blood I-Hg was correlated with that in maternal blood. The results show the importance of speciation of Hg in blood for evaluation of exposure and health risks.

Adult↗
PubMed2000

Outcome scores in degenerative cervical disc surgery.

Forty-six consecutive patients with neck pain and arm radiculopathy were treated with anterior cervical discectomy and fusion. All patients had neurological symptoms corresponding to a herniated disc and/or spondylosis at one or two cervical levels, verified by magnetic resonance imaging. The patients were stabilized with an anterior graft and randomized to either fixation with a CSLP plate or no internal fixation. Preoperatively and 2 years postoperatively the patients filled in a questionnaire that included a modified Million Index, a modified Oswestry Index and the Zung Depression Scale. They were also asked to register their pain in the arm and in the neck on a vertical visual analogue scale (VAS). At the 2-year follow-up, an unbiased observer graded the patients' clinical outcome using Odom's criteria. A test-retest procedure was carried out to examine the questionnaire reproducibility. In the group that was operated at one level, there was no significant improvement in any of the scores. Nevertheless, 81% of the patients were satisfied with the outcome of the surgery. All scores improved in the group operated at two levels. The pain in the neck and arm, as measured on a VAS, decreased in both groups. The improvement in arm pain was significantly more pronounced in patients operated with a plate at two levels compared to those who were operated without a plate. At the 2-year follow-up, patients with an excellent or good result according to Odom's criteria had a lower Million Index (P < 0.0005), Oswestry Index (P < 0.0005), and Zung (P = 0.024) score, than the group classified as fair or poor. There was a significant correlation (P < 0.0001 for all scores) between the test and retest results. We conclude that the modified Million Index and Oswestry Index are clinically useful tools in the evaluation of outcome after degenerative cervical disc surgery. The clinical benefits of plate fixation were minimal. The outcome after surgery, measured with the Oswestry Index, Million Index and VAS for arm and neck pain, seems to correlate well with the classification of outcome by Odom.

Adult↗
PubMed2000

Long-term cardiac mortality following radiation therapy for Hodgkin's disease: analysis with the relative seriality model.

PURPOSE: (a) To assess the increased risk of death due to ischemic heart disease (IHD) in a group of patients treated for Hodgkin's disease (HD) with radiation therapy (RT) as the primary treatment. (b) To quantify the dose response of IHD using a biophysical model. MATERIALS AND METHODS: Patient material consisted of 157 patients diagnosed for HD between 1972 and 1985 who received RT as the primary treatment at Radiumhemmet, Karolinska Hospital. The general population formed the control group. The RT treatments were reconstructed based on the individual treatment data and simulator films. Individual clinical and dosimetrical data were analyzed with the relative seriality model. The material was also analyzed grouping the material according to dose-volume constraints. RESULTS: Of the 157 patients, 13 (8.3%) died due to IHD. The standardized mortality ratio (SMR) was 5.0 (95% CI, 2.7-8.6). Analysis of dose-volume histograms (DVH) showed an increasing risk with increasing dose to a larger volume fraction. The observed individual clinical complication data could not be modeled unambiguously. The group analysis resulted in the dose-response parameters: D(50)=71 Gy, gamma=0.96 and s=1.0. CONCLUSIONS: A significantly increased risk of death due to IHD following RT for HD was found. The risk was found to increase with higher dose and larger volume fraction irradiated.

Adolescent↗
PubMed1999

Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families.

Eight Utah multigenerational families, each with three to six cases of schizophrenia, were phenotyped with two specific measures of inhibitory neurophysiological functioning, P50 auditory sensory gating (P50), and antisaccade ocular motor performance (AS). A genomewide linkage analysis was performed to screen for loci underlying a qualitative phenotype combining the P50 and AS measures. For this composite inhibitory phenotype, the strongest evidence for linkage was to the D22s315 marker on chromosome 22q (lod score = 3.55, theta = 0) under an autosomal dominant model. Simulation analyses indicate that this 3.55 lod score is unlikely to represent a false positive result. Lod scores were 2.0 or greater for markers flanking D22s315. A nonparametric linkage (NPL) analysis of the chromosome 22 data showed evidence for allele sharing over the broad region surrounding D22s315 with a maximum NPL score of 3.83 (p = .002) for all pedigrees combined.

Acoustic Stimulation↗
PubMed1999

Property damage and public disorder: their relationship with sales of alcohol in New South Wales, Australia.

It has been suspected for some time that alcohol is involved in the origin of offensive behaviour and property damage incidents. Using regression analyses and a cross-sectional design, this study investigates these relationships for both Sydney and country New South Wales (NSW), whilst controlling for key social and demographic variables. The study found that both offence types occurred more frequently in areas with greater sales of alcohol. The effect of alcohol sales was considerably larger in Sydney than it was in country NSW. There was an interaction between aboriginal population size and alcohol sales for country NSW offensive behaviour data. Overall, these findings are consistent with alcohol consumption playing a causal role in these offences, however, the possibility remains that alcohol sales may be acting as an indicator of criminal opportunity.

Age Factors↗
PubMed1999

Fluctuations in heroin purity and the incidence of fatal heroin overdose.

In order to determine the role played by heroin purity in fatal heroin overdoses, time series analyses were conducted on the purity of street heroin seizures in south western Sydney and overdose fatalities in that region. A total of 322 heroin samples were analysed in fortnightly periods between February 1993 to January 1995. A total of 61 overdose deaths occurred in the region in the study period. Cross correlation plots revealed a significant correlation of 0.57 at time lag zero between mean purity of heroin samples per fortnight and number of overdose fatalities. Similarly, there was a significant correlation of 0.50 at time lag zero between the highest heroin purity per fortnight and number of overdose fatalities. The correlation between range of heroin purity and number of deaths per fortnight was 0.40. A simultaneous multiple regression on scores adjusted for first order correlation indicated both the mean level of heroin purity and the range of heroin purity were independent predictors of the number of deaths per fortnight. The results indicate that the occurrence of overdose fatalities was moderately associated with both the average heroin purity and the range of heroin purity over the study period.

Adolescent↗
PubMed1999

The relationship between alcohol sales and assault in New South Wales, Australia.

AIMS: This paper explores the relationship between alcohol sales and assault in New South Wales (NSW), Australia. DESIGN: The design was a cross-sectional analysis of the relationship between alcohol sales and assault, taking into account spatial autocorrelation. SETTING: The analyses were carried out separately on data from metropolitan Sydney and country NSW. PARTICIPANTS: The unit of analysis was local government areas (178 in NSW). MEASUREMENTS: The dependent variable was assault rates. The independent variables were overall alcohol sales and sales disaggregated by alcohol and outlet type and relevant demographic and socio-economic factors. FINDINGS: Multiple regression analyses revealed a significant relationship between overall alcohol sales in an area and its incidence of assault for both Sydney and country NSW. There were few effects of outlet or alcohol type for Sydney, but the effect of alcohol sales from hotels and off-licences accounted for most of the alcohol-assault relationship for country NSW. CONCLUSIONS: Although the current research cannot exclude an opportunity account of the role of alcohol in assault, the results are entirely consistent with alcohol consumption as a causal agent.

Alcohol Drinking↗
PubMed1999

A novel missense mutation in the human plasmin inhibitor (alpha2-antiplasmin) gene associated with a bleeding tendency.

Heterozygosity for a G --> A mutation converting Val384(GTG) to Met(ATG) associated with plasmin inhibitor (alpha2-antiplasmin) deficiency was identified in three family members with bleeding tendency. The proband had traumatic breast haematoma and per-/postoperative bleeds. An affected daughter required a blood transfusion after a normal delivery and a son had prolonged bleeding after tooth extraction. The plasma plasmin inhibitor activities of the affected family members were reduced to 49-66% of normal. The antigenic concentrations determined by electroimmunoassay were reduced to 57-68% of normal. Crossed immunoelectrophoresis of plasma from the proband showed a normal pattern. The amino acid Val384 is located eight residues C-terminal (P8') of the P1 residue (Arg376) in the reactive site. The P8' residues of bovine and mouse plasmin inhibitor are both Val. Among other serpins the P8' residue is unconserved. The mutation was not present in the non-affected family member or 30 blood donors. In addition to the Val384Met mutation two new polymorphisms Ala-26(GCG)/Val(GTG) and Arg407(AGG)/Lys(AAG) and one previously reported polymorphism Arg6(CGG)/Trp(TGG) were identified in the plasmin inhibitor gene of the family. The allelic frequencies among 30 blood donors with normal values of plasma plasmin inhibitor (functional) were 0.84/0.16 for C/T in codon -26, 0.81/0.19 for C/T in codon 6 and 0.83/0.17 for G/A in codon 407.

Adult↗
PubMed1999

The Olerud Cervical Fixation System; a study of safety and efficacy.

To evaluate safety and efficacy of the Olerud Cervical Fixation System a one-year follow up study was done by an independent observer. There were 30 patients (14 women) with a mean age of 68 (37-85) years. Indications were rheumatoid arthritis in 10, spinal stenosis in 6, trauma in 6, metastases in 4, revisions in 3, and painful spondylotic deformity in one patient. Short fusions were performed in 8 patients and long fusions in 22. Four patients were fused to occiput. C1-C2 fusion was performed in 3 patients. Nineteen of the 20 still alive were evaluated at follow up. One patient was deliberately fused in hyperlordosis, in the rest the alignment was acceptable. Primary stabilization was achieved in all but one. 107 pedicle screws were used; one screw in Th2 was placed lateral to the pedicle. 42 subaxial transarticular screws were used. There were no complications related to these screws. One patient experienced a non-instrument related neurological deterioration. Two infections and one hematoma drainage healed on conservative treatment. Loss of fixation and non-union developed in 2 patients. Patients with metastasis or myelopathy due to rheumatoid arthritis carried a high mortality risk. The Olerud Cervical Spine Fixation System is versatile in posterior fixation of the cervical spine and has proven to be both safe and efficient.

Adult↗
PubMed1998

[Comparison of conventional PAP smears with thin layer specimen (liquid-based PAP test) and correlation with cytopathological findings with HPV status using the hybrid capture system].

Cervical smears of 554 outpatients of a hospital were examined using a blinded, split sample match pair protocol for which a conventional PAP-smear (CS) was first prepared with Cervex brush and the reminder of the sample was used for the thin-layer-preparation (TLP) according to the manual CytoRich System. The preparations of the two methods were compared with respect to quality and to sensitivity for atypias. In addition the HPV status was determined on the same cell suspension in cases with borderline changes (BLC) and dysplasias including carcinoma using the Hybrid Capture System. The use of TLP reduced the proportion of suboptimal preparations by more than 50% (14.6% vs. 35%) and eliminated the only inadequate preparation registered in CS. The DSP detected more than twice as many dysplasias of all degrees as CS (3.4% vs. 1.4%) and reduced the proportion of BLC to one third (3.2% vs. 9.6%). The percentages of cases positive for high- and intermediate-risk HPV in preparations with BLC, LSIL and HSIL were 17, 62.5% and 100% respectively. The TL-method improves significantly the efficiency of PAP-smears and allows the typing of HPV which is of clinical importance for the management of low grade squamous intraepitelial lesions and borderline changes. The findings speak against the further use of CS for cervical screening.

Adolescent↗
PubMed1998

The absorption, blood levels, and excretion of mercury after a single dose of mercury vapor in humans.

Nine healthy volunteers without amalgam fillings were exposed to 400 micrograms/m3 mercury vapor (Hg0) for 15 min, corresponding to 5.5 nmol Hg0/kg body wt (median range: 4.4-7.2). Frequent sampling of blood, urine, and exhaled air was performed for 30 days after exposure. The median retention of Hg0 was 69% of the inhaled dose. During the first 3 days after exposure 7.5-12% of the absorbed dose was lost by exhalation, with the median half time of Hg0 in expired breath being 2.0 days. In blood and plasma, a rapid absorption phase of Hg was seen, followed by a biexponential decline of the curves in both media. A substantial interindividual variation was observed in the area under the concentration-time curves of Hg in blood and plasma. In plasma the median half time of the second phase was 10 days. About 1.0% of the absorbed Hg was excreted via urine during the first 3 days after exposure, whereas the estimated amount excreted during 30 days ranged from 8 to 40%. In order to evaluate the chronic exposure to mercury from dental amalgam in the general population, the daily Hg dose from the fillings were estimated based on the plasma Hg levels found in subjects with amalgam fillings and on the plasma Hg clearance obtained in the present study. The daily Hg dose was estimated to 5-9 micrograms/day in subjects with an ordinary number of amalgam fillings.

Absorption↗
PubMed1998

Plate fixation adds stability to two-level anterior fusion in the cervical spine: a randomized study using radiostereometry.

This study evaluated whether addition of a cervical spine locking plate (CSLP) in two-level disc fusions improved the postoperative stability and reduced the time to healing. Radiostereometric analysis was used to obtain precise recordings of the three-dimensional motion between the fused vertebrae. Eighteen consecutive patients were operated on with excision of two adjacent cervical discs and anterior horseshoe grafting with autologous bone (Smith Robinson technique). Nine patients were randomized to stabilization with autologous bone grafting and CSLP plate fixation and nine patients to grafting without fixation. Clinical symptoms in terms of pain in the neck and the arm were analysed preoperatively and after 1 year using a visual analogue scale (VAS). The patients operated without a plate displayed increased rotations around the transverse axis, corresponding to the development of a kyphosis [mean value no plate/plate 14.4 degrees/0.8 degrees (repeated measure ANOVA: P < 0.01)]. The mean compression was 3.2 mm larger in patients operated without a plate (repeated measure ANOVA: P < 0.01). Patients operated without a plate had more arm pain at the 1-year follow up (P < 0.05, Mann-Whitney U test). The VAS score for neck pain did not differ significantly between the two groups. Plate fixation could not be demonstrated to increase the healing rate, promote more rapid fusion or influence the frequency of graft complications.

Adult↗
PubMed1998

Analysis of chromosome 6 markers in eight Utah schizophrenia pedigrees.

Eight multiplex Utah schizophrenia pedigrees were screened for linkage by applying a non-parametric linkage program, GENEHUNTER, using 30 chromosome 6 DNA markers. The overall maximum NPL score of the combined pedigrees was 1.50 (P = 0.079) at marker D6s281, located near the q terminus. The highest overall maximum NPL score for an individual pedigree was 2.81 (P = 0.043). In the chromosome 6p region, where numerous positive findings have been reported, we obtained no positive results.

Chromosomes, Human, Pair 6↗