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Biomedical subjects

A Jeppsson

Publications and source records attributed to A Jeppsson.

At least 19 recordsLinked to original sources

In vivo MR imaging of magnetically labeled human embryonic stem cells.

INTRODUCTION: Human embryonic stem cells (hES) have emerged as a potentially new therapeutic approach for treatment of heart and other diseases applying the concept of regenerative medicine. A method for in vivo visualization and tracking of transplanted hES would increase our understanding of in vivo hES behavior in both experimental and clinical settings. The aim of this study was to evaluate the feasibility of magnetic labeling and visualization of hES with magnetic resonance imaging (MRI). METHODS: hES were established and expanded according to standard procedures. After expansion, the cells were cultured under feeder free conditions and magnetically labeled by addition of dextran-coated Ferrum-oxide particles (Endorem) to the medium. Accumulation of small particles of iron-oxide (SPIO) in hES was assessed by Prussian blue staining and electron microscopy. For in vitro MRI, the labeled and unlabeled hES were examined in cell solution and after transplantation into explanted mouse heart ( approximately 100,000 cells) on a Bruker Avance DMX 500 vertical magnet at 11.75 T. A multi-slice, multi spin-echo T(2)-weighted images were obtained. For in vivo imaging, the experiments were performed on male Sprague-Dawley using Bruker Biospec 2.35 T magnet. The hES were directly injected ( approximately 500,000 cells) after surgical procedure (thoracotomy) into anterior left ventricular (LV) wall. Multi-slice T(2)-weighted gradient echo images were obtained using cardiac gating. RESULTS: hES appeared to be unaffected by magnetic labeling and maintained their ability to proliferate and differentiate. No additive agent for membrane permeabilisation was needed for facilitation of intracellular SPIO accumulation. Prussian blue and electron microscopy have revealed numerous iron particles in the cytoplasm of hES. On T(2)-weighted images, the labeled cells have shown well-defined hyopintense areas at the site of injection in anterior LV wall both in vitro and in vivo. CONCLUSIONS: It is feasible to magnetically label and visualize hES both in vitro and in vivo. MR visualization of magnetically labeled hES may be a valuable tool for in vivo tracking of hES.

Animals↗

Expanding the donor pool: lung transplantation with donors 55 years and older.

The scarcity of donor organs is one of the major limitations to lung transplantation. This has led to a progressive expansion of criteria for donor selection in lung transplantation. This study evaluated the outcome of recipients of lungs from donors >/=55 years. We performed a retrospective analysis of 212 consecutive lung transplantations. Recipients were divided into two groups, those receiving lungs from donors >/=55 years (older donor group) and those receiving lungs from donors <55 years (younger donor group). Recipient baseline characteristics, time in the intensive care unit (ICU), early mortality, and long-term survival (Kaplan-Meier) were compared between the groups. Forty-one donors (19%) were >/=55 years. Mean recipient age in the older donor group was higher than in the younger donor group (52 +/- 8 vs. 47 +/- 12 years; P = .015). Indication for transplantation did not differ between the groups. ICU stay was comparable between the two groups (6 +/- 12 vs. 7 +/- 11 days; P = .64). Actual 30-day mortality (10.8% vs. 6.4%; P = .32), 1-year mortality (17.1 vs. 19.6%; P = .50), and cumulative long-term survival (65% and 62% at 5 years, P = 1.00) did not differ between the older and younger donor group. This study indicated that transplantation of lungs from selected donors aged >/=55 years did not impair short-or long-term results. The use of lungs from elderly donors may help to increase the number of donor organs for lung transplantation.

Age Factors↗

Long-term outcome in heart failure patients evaluated for heart transplantation but considered too well.

Patients referred for heart transplantation evaluation may be accepted for transplantation, or denied due to existing contraindications or judged to be too well. There is little knowledge about long-term outcome in patients considered too well for transplantation. Ninety-five patients (mean age 47 +/- 12 years, 73% men) judged "too well" at evaluation were included in this study. Acceptance for transplantation followed international guidelines. The follow-up (mean 4.5 years) was complete. Twenty of the 95 patients (21%) were eventually accepted for transplantation during the follow-up period. Twenty-one patients (22%) died, 13 without preceding acceptance for transplantation, 4 on the waiting list for transplantation, and 4 after transplantation. Cumulative and transplant-free survival at 1, 5, and 10 years were 91%, 82%, and 65%, and 90%, 70%, and 50%, respectively. In conclusion, long-term survival in patients considered too well for transplantation is better than in most contemporary series of heart transplant recipients, which suggests that the guidelines for acceptance are appropriate. However, almost one fifth of the patients die without preceding acceptance for transplantation or while on the waiting list, which illustrates the need for frequent reevaluation and tools to identify heart failure patients with an increased risk for sudden death.

Adult↗

Turnover of trypanosomal ornithine decarboxylases.

Interestingly, there is a major difference in turnover rate between ornithine decarboxylases (ODCs) from various trypanosomatids. ODCs from Trypanosoma brucei and Leishmania donovani are both stable proteins, whereas ODC from Crithidia fasciculata is a metabolically unstable protein in the parasite. C. fasciculata ODC is also rapidly degraded in mammalian systems, whereas the closely related L. donovani ODC is not. The degradation of C. fasciculata ODC in the mammalian systems is shown to be dependent on a functional 26 S proteasome. However, in contrast to the degradation of mammalian ODC, the degradation of C. fasciculata ODC does not involve antizyme. Instead, it appears the degradation of C. fasciculata ODC may be associated with poly-ubiquitination of the enzyme.

Animals↗

The importance of grade 2 ischemic mitral regurgitation in coronary artery bypass grafting.

OBJECTIVE: To study if grade 2 ischemic mitral regurgitation (MR) influences outcome after coronary artery bypass grafting (CABG). METHODS: Results of all CABG patients with grade 2/4 ischemic MR operated during 1995--1998 (n = 89) were compared with all CABG patients without MR (n = 4709) during the same period. To further evaluate patients with grade 2 ischemic MR, a case-control study focusing on functional status was performed. Control patients without MR (n = 89) were matched for age, gender and left ventricular ejection fraction. All patients were interviewed regarding angina symptoms and functional status. RESULTS: Survival according to Kaplan--Meier at 1 and 3 years were inferior in the MR group compared to all CABG patients (91 vs 96% and 84 vs 92%, respectively (P = 0.0017). However, MR patients were older (68 +/- 9 vs 65 +/- 9 years (mean +/- SD), P = 0.008) and had an inferior preoperative left ventricular ejection fraction (42 +/- 14 vs 58 +/- 14%, P < 0.0001). In the case-control study, New York Heart Association (NYHA) class and Higgins' risk score differed preoperatively between the MR group and controls. Neither 30-day mortality (4,5% in both groups) nor survival at 1 (91 vs 93%) and 3 years (84 vs 88%) differed significantly. NYHA class and angina class (Canadian Cardiovascular Society, CCS) improved similarly in both groups. Postoperatively, 62% of the patients in the MR group had reduced, 36% unchanged and 2% increased MR. CONCLUSIONS: CABG on patients with grade 2 ischemic MR reduces angina pectoris and improves functional status to the same extent as in CABG patients without MR. Postoperative morbidity and mortality do not differ significantly between the groups. Grade of MR is reduced or unchanged after CABG in patients with grade 2 ischemic MR. The study supports an operative strategy where grade 2 ischemic mitral regurgitation is treated by CABG alone but the result do not exclude that there might be individual patients that would benefit from a valvular or annular procedure in combination with CABG. How these patients should be identified remains unclear.

Aged↗

Insulin (GIK) improves central mixed and hepatic venous oxygenation in clinical cardiac surgery.

OBJECTIVE: Insulin is a vasodilating agent and it was hypothesized that insulin (GIK) could improve systemic and regional oxygenation in cardiac surgery with cardiopulmonary bypass (CPB). Two questions were addressed: 1) Does insulin improve central mixed and hepatic venous oxygenation during CPB? and 2) Does this treatment reduce systemic levels of the proinflammatory mediators C3a and IL-6? DESIGN: Prospective, randomized, controlled study at a university hospital. Thirty patients were included and 16 of these received an infusion of insulin, glucose and potassium (GIK) using an euglycemic clamp technique. The insulin infusion was started during hypothermia, 15 min before rewarming. Blood gases and hemodynamic parameters were measured during hypothermia (before the insulin infusion was started), during rewarming at 35 degrees C, and 30 min after CPB was discontinued. Inflammatory markers were measured: preoperatively, during hypothermia and 2 h after CPB. RESULTS: GIK was associated with reduced systemic vascular resistance (p = 0.02 vs the control group), higher bypass pump flow (p = 0.001). higher central mixed oxygen saturation (p = 0.036) and oxygen tension (p = 0.001) and higher hepatic venous oxygen saturation (p = 0.04) and oxygen tension (p = 0.006). C3a and IL-6 increased during surgery in both groups but there were no differences between the groups. CONCLUSION: 1) GIK infusion improved central mixed and hepatic venous oxygenation in patients undergoing heart surgery. 2) During the conditions of this study, this had no effect on the proinflammatory mediators C3a and IL-6.

Aged↗

Financial priorities under decentralization in Uganda.

This paper explores changes to budget allocations for health during the decentralization process in UGANDA: When the districts were given the authority to allot their own budgets, allocations for health were reduced considerably. The rationale for this by district leaders is investigated and analyzed. Their criteria for budget allocations for health are often based on views different to those held at central level, hence there can be conflict between the two. The mechanisms instituted by central government in reaction to what was perceived as a lack of local support to the health sector are described. In conclusion, while conditional funding may be a useful short-term step, long-term development requires less conditionalities. Health professionals need to work closely with local leaders and district officials to make health a political priority in order to develop and allocate resources for health at local level.

Budgets↗

The policy on public-private mix in the Ugandan health sector: catching up with reality.

An informal public-private mix in the health sector has always existed in Uganda, and policymakers, planners and the public in general have taken this for granted. There is now renewed effort to develop a comprehensive policy on the mix, but the policy process has proved to be tortuous and the mix has been interpreted differently by different stakeholders. While significant differences in opinion on the mix still remain, it is becoming clear that the new policy should enable health institutions, whether in the public or the private sector, to play roles in which they have clear comparative advantage over others.

Cooperative Behavior↗

Aortic surgery in patients with marfan syndrome: long-term survival, morbidity and function.

BACKGROUND AND AIM OF THE STUDY: The natural history of patients with Marfan syndrome is depressing, but surgical intervention on the aorta can improve the prognosis. Study results were analyzed with reference to long-term survival, morbidity and function. METHODS: Seventy-four Marfan patients (51 males, 23 females; mean age 41+/-14 years), underwent first-time aortic surgery between 1977 and 1998. Follow up information regarding mortality, morbidity and functional status was obtained from patient records and by questionnaire. The mean follow up was 5 years (range: 0-19 years). Forty-seven patients (64%) had a dissection, 27 (36%) an aneurysm, and 45 (61%) patients underwent emergency operations (<4 h from arrival at hospital). In 72 patients (97%) the disease affected the ascending aorta, and implantation of a composite graft was the most frequent operation. RESULTS: Overall 30-day mortality was 12% (3% in elective cases, 18% in emergency cases, p <0.05). Emergency operations and surgery extended to the aortic arch were risk factors for early mortality. Overall actuarial survival was 63.4+/-8% at 10 years. Age was the only risk factor for late mortality. Seventeen patients were reoperated on due to pathologies of the remaining aorta (n = 12), pseudoaneurysms (n = 4) and aortic valve endocarditis (n = 1). A total of five patients had endocarditis; one patient with a homograft required surgery, and medical treatment was successful in the other four patients. Five patients had neurological thromboembolic episodes without permanent damage, and six had minor bleeding complications. Freedom from early and late mortality, reoperation on the aorta and major cardiovascular events (endocarditis episodes, thromboembolic/hemorrhagic strokes and other major bleeding/embolic episodes) was 33.3 +/- 8.1% at 10 years. At follow up, 98% of patients were in NYHA functional class I or II, and 80% were working. CONCLUSION: Elective aortic surgery in Marfan patients can be performed with good results. Close follow up of patients undergoing surgery is important. The long-term functional status of surviving patients is satisfactory.

Adolescent↗

Gene transfer of endothelial nitric oxide synthase to pulmonary allografts: impact on acute rejection.

Experiments were designed to study whether overexpression of nitric oxide (NO) from endothelial nitric oxide synthase (eNOS) affects acute rejection. Allogenic, orthotopic single-lung transplantation was performed after transbronchial adenoviral-mediated gene transfer (3 x 10(8) pfu) of either of eNOS or beta-galactosidase to donor lungs of rats (n = 6 each). No immunosuppression was used. After 4 days, transplanted lungs were prepared for enzyme activity, cGMP and histology. Calcium-dependent NOS activity, reflecting eNOS, was greater in eNOS-transduced lungs (587 +/- 97 vs 2.1 +/- 1.4 pmol/mg protein per h, P <0.001). In contrast, calcium-independent NOS activity, reflecting iNOS, was comparable. Concentrations of cGMP were higher in eNOS-transduced lungs (13.2 +/- 2.3 vs 4.9 +/- 0.5 pmol/mg protein). Positive immunostaining for eNOS was present in pneumocytes only in eNOS-transduced lungs. No difference in histological grade of rejection was observed. eNOS gene transfer to pulmonary allografts results in a functionally active transgene product and increased NO production. Increasing NO from eNOS does not affect histogically identified acute rejection.

Adenoviridae↗

Improved efficiency of gene transfer to the transplanted lung by retrograde vascular gene delivery.

Experiments were designed to evaluate the efficiency of antegrade compared to retrograde vascular gene transfection of donor lungs used for transplantation. Rat donor lungs (n = 5/group) were transduced with an adenoviral vector encoding for beta-galactosidase (AdbetaGal), either antegrade in the pulmonary artery (Group A, 3 x 10(8) pfu, Group B, 3 x 10(9) pfu) or retrograde into the pulmonary vein (Group C, 3 x 10(8) pfu), immediately after pneumoplegia. After storage at 4 degrees C for 1 h, the transduced lungs were transplanted orthotopically in syngeneic animals. The lungs were assessed for transgene expression by ELISA and X-Gal-staining at day 7 after operation. Inflammation was graded based on the extent of inflammatory cell infiltration. Transgene expression was similar between Groups A (1.7 +/- 0.7 ng/mg protein) and B (2.1 +/- 1.0 ng/mg protein). With retrograde delivery, there was a four-fold (8.3 +/- 2.6 ng/ mg protein) increase (P < 0.05) in transgene expression compared to either group A or B. In all groups, pneumocytes were transduced most frequently. The degree of inflammation correlated positively with the extent of transgene expression (r = 0.75, P < 0.01). The efficiency of vascular gene delivery to transplanted lungs can be improved by retrograde delivery of the vector via the pulmonary vein. Transgene expression predominates in pneumocytes following both antegrade and retrograde delivery. The severity of inflammation in the transplanted lung appears to correlate with the extent of transgene expression.

Adenoviridae↗

Ectopic metaplastic ossification after sternotomy.

Ectopic ossification is a rare complication after a major operation. We report a case of cutaneous infection and metaplastic ossification in an 80-year-old man who underwent coronary artery bypass grafting 4 years earlier. Computed tomographic scan demonstrated a partial pseudarthrosis of the corpus sterni. The infected part of the sternal scar was excised and sternal wires were removed. Eight months later, the wound has healed without complications and the cutaneous ossification is unaltered.

Aged↗

Highly efficient ex vivo gene transfer to the transplanted heart by means of hypothermic perfusion with a low dose of adenoviral vector.

BACKGROUND: Hypothermic conditions required for donor heart preservation may reduce gene-transfer efficiency. Experiments were designed to determine whether a perfusion technique could improve the efficiency of gene transfer to donor hearts. METHODS: An adenoviral vector encoding beta-galactosidase (3.5 x 10(8) plaque-forming units) was infused into explanted rat hearts under 4 conditions (each n = 6): (1) the virus was diluted in 350 microL of University of Wisconsin solution and infused as a high-pressure bolus into the coronary arteries of donor hearts through the aortic root; (2) the virus was diluted in 5 mL of University of Wisconsin solution and circulated by means of a peristaltic pump (flow, 0.75 mL/min) through the vasculature of the donor heart for 30 minutes; (3) 5 mL of viral solution was circulated as for group 2 for 15 minutes; and (4) 5 mL of viral solution was circulated for 5 minutes at a flow rate of 2.4 mL/min. Transduced hearts were transplanted into the abdomen of syngeneic rats, and transgene expression was assessed by means of immunoassay 4 days later. RESULTS: The median beta-galactosidase content was (1) 45.0 ng/mg protein (25th-75th percentile, 33-73 ng/mg), (2) 640 ng/mg protein (25th-75th percentile, 614-878 ng/mg), (3) 493.8 ng/mg protein (25th-75th percentile, 456-527 ng/mg), and (4) 503.3 ng/mg protein (25th-75th percentile, 475-562 ng/mg; P <.01 for group 2 vs group 1, and P <.05 for groups 3 and 4 vs group 1). Transgene expression was predominantly in myocytes and favored the subepicardial region of the right ventricle. CONCLUSION: Hypothermic perfusion of the donor heart with an adenoviral vector resulted in efficient transgene expression compared with that induced by a single bolus injection.

Adenoviridae↗