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Biomedical subjects

H Manninen

Publications and source records attributed to H Manninen.

At least 19 recordsLinked to original sources
PubMed2003

Transfection of oocytes and other types of ovarian cells in rabbits after direct injection into uterine arteries of adenoviruses and plasmid/liposomes.

Transfection of oocytes should be avoided in somatic gene therapy. However, several viral vectors including adenoviruses can transfect zona-pellucida-free eggs in vitro. During early stages of development, oocytes of postnatal ovaries lack the zona pellucida. Therefore, they may be susceptible to gene transfer and unintended toxic effects. The purpose of this study was to see whether the injection of adenoviruses (1 x 10(10) PFU) or plasmid (500 microg)/DOTMA:DOPE (1:2) liposomes directly into uterine arteries in pregnant rabbits leads to transfection of oocytes and other types of ovarian cells. LacZ and herpes simplex virus thymidine kinase (HSV-TK) were used as transgenes. It was found that both adenovirus and plasmid vectors transfected oocytes at the primordial and primary follicle stage when they were not protected by the zona pellucida, whereas no transfection was seen in oocytes surrounded by the zona pellucida. Efficient transfection of corpus luteum and granulosa cells was also detected by adenoviral and plasmid vectors. Transfection of oocytes and other ovarian cells was verified by X-gal staining and laser microdissection, followed by PCR analysis. HSV-TK gene transfer, followed by ganciclovir treatment, led to destruction of a significant number of oocytes, whereas HSV-TK gene transfer alone did not lead to toxic effects. It is concluded that the presence of a high concentration of adenovirus or plasmid vectors via the uterine artery may lead to transfection of zona-pellucida-free oocytes and other ovarian cells.

Adenoviridae↗
PubMed2002

Endovascular treatment of aortic aneurysms in Finland: the first four years' experience.

BACKGROUND AND AIMS: In this study the results of endovascular treatment of aortic aneurysms in Finland are presented and compared to the results of the Eurostar registry. MATERIAL AND METHODS: A total of 229 patients with aortic aneurysm were treated in five different Finnish centres during 1996-2000. The data of these patients were collected prospectively by surgeon or interventional radiologist involved. During the same period of time 2464 patients were registered in the Eurostar registry. RESULTS: The procedure was performed successfully in 97% of patients in Finland, and the 30-day mortality was 0,9%. A graft limb thrombosis was detected in 9% of the patients in Finland. A permanent primary endoleak at the first 30-day control was seen in 23 patients (10%). During the follow-up 17 secondary endoleaks (7%) were detected. A secondary intervention was necessary in 26% of the patients. Three patients (1.3%) had late rupture of the abdominal aortic aneurysm. CONCLUSIONS: According to the Finnish short-time results, endovascular treatment of aortic aneurysms is safe and associated with relatively low morbidity and mortality. The mid-term results are more disappointing with relatively many graft thromboses and endoleaks, and a frequent need of secondary interventions.

Adult↗
PubMed2001

Angiographically guided utero-placental gene transfer in rabbits with adenoviruses, plasmid/liposomes and plasmid/polyethyleneimine complexes.

We examined the feasibility of gene transfer to rabbit placenta using adenoviruses, plasmid/liposomes and plasmid/polyethyleneimine (PEI) complexes. Pregnant New Zealand White rabbits (n = 17) were anesthetized and local gene transfer was done via a catheter inserted in uterine arteries under direct angiographic control. Either nuclear targeted LacZ adenoviruses (1.0 x 10(10) p.f.u.), nuclear targeted LacZ plasmid (500 microg)/liposome (DOTMA:DOPE 1:1) complexes or nuclear targeted LacZ plasmid (250 microg)/PEI (25 kDa) complexes (charge ratio +/-4) were used. Animals were killed 3 days later and detection of the transgene expression was done by X-gal staining and RT-PCR. Adenovirus-mediated gene transfer resulted in a high transfection efficiency (34 +/- 10%) in placental trophoplastic cells. Very little, if any, transfection was seen in fetal membranes. Plasmid/liposomes and plasmid/PEI complexes led to a very low (<0.01%) transfection efficiency in trophoblastic cells, but some transfection was seen in fetal membranes. A total of 25 fetuses were analyzed for the presence of transgene at the time of death. In most fetuses expression of the LacZ gene was below the sensitivity of the X-gal staining, but expression was detected by PCR in 50%, 50% and 42% of the analyzed fetuses after adenoviral, plasmid/PEI and plasmid/liposome gene transfer, respectively. No major inflammatory changes were present in the transfected placentas as analyzed by general histology and macrophage- and T cell-specific immunostainings. We conclude that catheter-mediated intravascular gene transfer with adenoviruses can be used for the transfection of placental trophoplastic cells, but plasmid complexes are inefficient for this purpose. However, selective angiographically guided gene transfer also led to leakage of the vector to fetuses. Therefore, if gene therapy is developed for the treatment of placental disorders, the gene-vector combination should not be harmful to the fetus and the expression of the transgene should only occur in placenta.

Adenoviridae↗
PubMed2001

Results of infrainguinal bypass surgery: an analysis of 263 consecutive operations.

BACKGROUND AND AIMS: The purpose of this clinical study was to assess the success of infrainguinal revascularization in the treatment of lower limb ischaemia. MATERIAL AND METHODS: 226 consecutive patients underwent 263 femoropopliteal (n = 194) or femorodistal (n = 69) bypass operations during 1988-1996 at a university hospital. Records of all patients were reviewed. Late control visits including clinical and colour doppler ultrasound examinations were programmed for 109 patients. Initial success, primary and secondary patencies, limb salvage and survival rates were determined and factors affecting outcome were analysed in various patient categories. RESULTS: Initial success rate was 92% (243/263). The primary and secondary patencies were 70/83% and 52/63% at one and five years, respectively. The corresponding limb salvage rates for patients with chronic critical ischaemia were 82% and 77%. The number of diseased vessels in the treated limb correlated negatively with the primary patency. Advanced age did not affect primary patency or limb salvage rates. Diabetes and the use of distal revascularizations were independent predictors of poorer limb salvage. Diabetes and renal insufficiency proved to shorten life expectancy. CONCLUSIONS: Infrainguinal revascularizations are effective regardless of patient's age. The extent of atherosclerotic changes in the operated limb, diabetes and renal insufficiency are factors affecting outcome.

Adolescent↗
PubMed2000

Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty.

Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronary arteries after percutaneous translumenal coronary angioplasty (PTCA) in a randomized, double-blinded, placebo-controlled study. The optimized angioplasty/gene delivery method was previously shown to lead to detectable VEGF gene expression in human peripheral arteries as analyzed from amputated leg samples. Gene transfer to coronary arteries was done with a perfusion-infusion catheter, using 1000 microg of VEGF or beta-galactosidase plasmid complexed with 1000 microl of DOTMA:DOPE liposomes. Ten patients received VEGF P/L, three patients received beta-galactosidase P/L, and two patients received Ringer lactate. Gene transfer to coronary arteries was feasible and well tolerated. Except for a slight increase in serum C-reative protein in all study groups, no adverse effects or abnormalities in laboratory parameters were detected. No VEGF plasmid or recombinant VEGF protein was present in the systemic circulation after the gene transfer. In control angiography 6 months later, no differences were detected in the degree of coronary stenosis between treatment and control groups. We conclude that catheter-mediated intracoronary gene transfer performed after angioplasty is safe and well tolerated and potentially applicable for the prevention of restenosis and myocardial ischemia.

Adult↗
PubMed2000

Disc degeneration and bone density in monozygotic twins discordant for insulin-dependent diabetes mellitus.

The effects of insulin-dependent diabetes mellitus on bone density and connective tissue degeneration have theoretical interest and practical relevance. Several experimental studies in animals have demonstrated the harmful effects of insulin deficiency on connective tissues. However, clinical studies in humans have produced somewhat contradictory results, most likely due to difficulties controlling for general degeneration and factors associated with diabetes. In nine pairs of monozygotic twins discordant for insulin-dependent diabetes mellitus, we compared femoral and lumbar bone mineral density (assessed by dual-energy x-ray absorptiometry) and spinal degeneration (assessed by magnetic resonance imaging). The bone densities were, on average, 0.1-0.3% lower (p = 0.87-0.96) in diabetic patients. However, after controlling for smoking, we found that the bone density in the femoral neck was 2.5% (0.025 g/cm2) lower in diabetic individuals than in their twins (p = 0.09). The five magnetic resonance imaging parameters used to evaluate disc degeneration did not differ between diabetic patients and their twins. In conclusion, our results provide no evidence that insulin-dependent diabetes mellitus has any major effect on bone density or disc degeneration.

Absorptiometry, Photon↗
PubMed1999

Computed tomography findings 4 years after surgical management of lumbar spinal stenosis. No correlation with clinical outcome.

STUDY DESIGN: A prospective, cross-sectional study of the correlation between postoperative computed tomography findings and patients' clinical outcomes approximately 4 years after laminectomy for lumbar spinal stenosis. OBJECTIVES: To evaluate clinical and radiologic characteristics and their relation to each other. SUMMARY OF BACKGROUND DATA: The goal of surgical management for lumbar spinal stenosis is to decompress the stenotic area determined in radiologic examinations to relieve pressure on the neurovascular structures. However, the success of this decompression very rarely has been confirmed by postoperative radiologic imaging or compared with clinical outcome. METHODS: Postoperative computed tomography was performed on 191 patients. The findings were classified as "no stenosis," "central stenosis," "lateral stenosis," or "central-lateral stenosis." Postoperative instability of the lumbar spine was investigated by functional radiography. Clinical status was assessed by clinical examination. Subjective disability was assessing using the Oswestry questionnaire, and severity of pain using the visual analog scale. Walking capacity was evaluated by the tread-mill test. RESULTS: Radiologic studies revealed postoperative stenosis in 123 patients (64%). Small differences between the computed tomography groups were shown for the Oswestry score, but not for walking distance. Clinical signs, severity of pain, and radiologic instability were very similar for all computed tomography groups. CONCLUSIONS: Postoperative radiologic stenosis was very common in patients operated on for lumbar spinal stenosis, but this did not correlate with clinical outcome. The clinician must be cautious when reconciling clinical symptoms and signs with postoperative computed tomography findings in patients operated on for lumbar spinal stenosis.

Disability Evaluation↗
PubMed1998

Adenovirus-mediated gene transfer to lower limb artery of patients with chronic critical leg ischemia.

Arterial gene transfer offers a promising new approach for the treatment of vascular disorders. However, no data are available about the gene transfer efficiency in human arteries in vivo. The aim of this study was to evaluate the safety and feasibility of catheter-mediated adenoviral gene transfer in human peripheral arteries. Ten patients (8 females, 2 males, mean age 80 +/- 8 years) suffering from chronic critical leg ischemia with a prior decision for amputation were recruited in the study. Gene transfer was performed in eight patients in conjunction with a conventional percutaneous transluminal angioplasty, using a perfusion coil balloon catheter. Two patients served as controls. Increasing concentrations of replication-deficient adenoviruses (titers from 1 x 10(8) to 4 x 10(10) PFU) containing a nuclear-targeted beta-galactosidase marker gene were administered into the arteries over 10 min via the catheter. Amputations were performed 20 to 51 hr after the procedures and gene transfer efficiency was evaluated in the transduced arteries using X-Gal staining for beta-galactosidase activity. Beta-galactosidase gene transfer was well tolerated and no adverse tissue responses or systemic complications were observed in any of the patients. Gene transfer was successful in six of the eight patients. Gene transfer efficiency varied between 0.04 and 5.0% of all arterial cells. Transgene expression was detected in smooth muscle cells, endothelial cells, and macrophages and in tunica adventitia. However, transgene activity was not evenly distributed in the arterial wall and no transgene activity was found beneath advanced atherosclerotic lesions. The safety and feasibility of in vivo gene transfer by adenoviral vectors to human peripheral arteries were established. Although improvements are still required in gene transfer efficiency, these findings suggest that adenoviruses can be used to deliver therapeutically active genes into human arteries.

Adenoviridae↗
PubMed1998

Subclinical cerebral complications after coronary artery bypass grafting: prospective analysis with magnetic resonance imaging, quantitative electroencephalography, and neuropsychological assessment.

OBJECTIVE: To analyze the frequency and severity of subclinical cerebral complications associated with coronary artery bypass grafting (CABG). DESIGN: A prospective controlled study using preoperative and postoperative magnetic resonance imaging (MRI) of the brain, quantitative electroencephalography (QEEG), and detailed neuropsychological and neurologic examinations as potentially sensitive indicators of subclinical cerebral injury associated with CABG. SETTING: Multimodality evaluation in a tertiary care unit (Kuopio University Hospital, Kuopio, Finland). PATIENTS: Thirty-eight patients undergoing elective CABG and 20 control patients undergoing other major vascular surgery, mostly operations on the abdominal aorta. MAIN OUTCOME MEASURES: Coronary artery bypass grafting-associated cerebral complications assessed preoperatively and postoperatively by brain MRI, QEEG, detailed neurologic examination, and a neuropsychological test battery that evaluates cognitive functions in major areas known to be vulnerable to organic impairment (learning and memory, attention, flexible mental processing, and psychomotor speed). RESULTS: There were no major neurologic complications. A mild hemisyndrome developed in 1 patient who underwent CABG and in 1 control patient. Overall, there was no decline in mean cognitive performance 3 months after surgery. Electroencephalographic slowing of 0.5 Hz or more in at least 2 channels occurred in 11 patients who underwent CABG and in 1 control patient (P=.03). The postoperative brain MRI scan revealed new small ischemic lesions in 8 patients (21%) in the CABG group but in none of the control group (P=.03). These new cerebral MRI lesions did not explain deterioration in neuropsychological test performance or the QEEG slowing. CONCLUSIONS: Coronary artery bypass grafting causes more QEEG alterations and small ischemic cerebral lesions that are detectable by MRI than does other major vascular surgery. The effect is mainly subclinical, because no statistically significant deterioration in mean neuropsychological test performance was detected.

Aged↗
PubMed1997

Movement disturbances of the lumbar spine and abnormal back muscle electromyographic findings in recurrent low back pain.

STUDY DESIGN: A cross-sectional analysis was done of patients with recurrent low back pain referring to the lower limbs. OBJECTIVES: To analyze dynamic radiographs of forward and backward bending of the lumbar back and to determine, using routine neurophysiologic measurements, the functional state of the lower nerve roots in patients with recurrent low back pain radiating to the lower limbs. METHODS: Clinical and neurophysiologic studies showed eight of the 108 patients with low back pain to have ventral root impingement at either L5 or S1 level. The remaining 100 patients, 56 women and 44 men (mean age, 37.6 years; range, 17-62 years), made up the study group for continuing investigation. History of low back pain ranged from 4 months to 20 years. RESULTS: Disturbed intervertebral movement was found in 51 of 100 patients. Twenty-seven percent had L5 or L4 anterolisthetic hypermobility, and 35% had L4 or L3 vertebral retrolisthesis. Vaguely delineated radiating sensations in the lower limbs were common (62%). Back muscle electromyographs were mostly (86%) normal in patients whose low back pain was localized. Conversely, almost three-fourths of those experiencing radiating or referred pain had abnormal electromyographs, consistent with a mild degree of axonal damage in the posterior branch of the lumbar nerve root innervating the medial paraspinal muscles. This finding was most common among patients with retrolisthesis and simultaneous degenerative changes. CONCLUSIONS: Evaluation of low back pain should include tests for degenerative retrolisthesis, especially in patients experiencing radiating sensations with no evidence of root impingement, because abnormal electromyographic findings showing denervation of the paraspinal muscles was most common in patients with degenerative retrolisthesis. To improve the functional support of the lumbar region, rehabilitation should be directed to the medial back muscles because they provide the most effective support for intervertebral motion and because mild disturbances appear to be associated with their innervation in recurrent low back pain.

Adolescent↗
PubMed1997

Lifetime exercise and disk degeneration: an MRI study of monozygotic twins.

Participation in some competitive sports has been shown to increase disk degeneration; however, the long-term effects of recreational physical activities are unclear. We investigated the effects of endurance exercise and power sports on disk degeneration in monozygotic male twins with contrasting lifetime exercise histories. The effects of endurance exercise were studied in 22 discordant twin pairs (mean lifetime frequencies of 3.9 vs 1.1 times/wk), and the effects of power sports were investigated in 12 discordant pairs (2,300 vs 200 h of weightlifting). The age range of the twins was from 35 to 69 yr. No differences in MRI findings between co-twins discordant for endurance exercise were found at any of the spinal regions. Subjects with more power sport involvement had greater disk degeneration in the T6-T12 region (P < 0.03), but similar findings were not present in the lumbar spine. Controlling for recalled back injuries, occupational loading, smoking, and driving did not significantly affect the results. No signs of beneficial or harmful effects of lifetime endurance exercise on disk degeneration were seen. Increased power sport participation was associated with slightly greater disk degeneration in the lower thoracic spine, but not in the lumbar spine.

Adult↗
PubMed1997

The association of trunk muscle cross-sectional area and magnetic resonance image parameters with isokinetic and psychophysical lifting strength and static back muscle endurance in men.

The relationship between trunk muscle morphology as measured on transverse magnetic resonance images and isokinetic lifting, psychophysical lifting, and static back muscle endurance testing was examined in 110 men, ages 35-67 years (mean, 48 years), who had been chosen based on their exposure to a wide variety of occupational and leisure-time physical activities. The computed T2-relaxation times and the T2-weighted and proton density-weighted signal intensities of the erector spinae, quadratus lumborum, and psoas major muscles had almost no association with any of the strength tests. The cross-sectional areas of the muscles had good correlations with isokinetic lifting strength (r = 0.46-0.53). They did not correlate well with psychophysical lifting and static back muscle endurance. Other characteristics or neurological or psychological factors may have more influence on those tests.

Adult↗
PubMed1997

Stent grafting for abdominal aortic aneurysms in Finland--a feasibility study.

BACKGROUND AND AIMS: Endovascular repair of abdominal aortic aneurysms (AAA) is a feasible procedure in selected patients. In order to assess how many AAAs are suitable for such a procedure, a survey has been conducted in Helsinki, Kuopio, and Tampere University Hospitals. MATERIAL AND METHODS: AAAs having a maximum diameter of 45 mm or more at ultrasonography were included for further evaluation and assessment by angiography and/or spiral CT angiography to determine the length and width of infrarenal aneurysmal neck as well as the dimensions of the distal abdominal aorta and iliac arteries. RESULTS: Among a total of 75 patients with AAA examined in three centres, ultrasonography overestimated the size of the aneurysm in 12 cases that were demonstrated by angiography and CT to have a diameter of less than 45 mm. Among those patients with larger aneurysms, 17 (27%) were suitable for endovascular repair. Stent grafting has been performed in 10 patients until May, 1997. Perigraft leakage occurred in one patient who required the insertion of an additional collar stent graft. CONCLUSIONS: Large numbers of suitable patients are not easy to find but, by performing joint screening in Finland, epidemiological data on suitable aneurysms and improving co-operation between centres can be achieved. Therefore, it would be wise to centralise endovascular repair of AAA.

Aortic Aneurysm, Abdominal↗