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Biomedical subjects

M Brandt

Publications and source records attributed to M Brandt.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of oligosaccharides on rejection and reperfusion injury after lung transplantation.

BACKGROUND: During rejection and reperfusion injury, infiltration of leukocytes into the lung allograft is regulated by adhesion molecules, especially selectins. Sialyl-Lewis X (SLX), an oligosaccharide, is a membrane ligand molecule of P-selectin adhesion receptors. In this study, we investigated the effect of intravenous administration of a synthetic oligosaccharide analog of SLX on rejection and reperfusion injury after rat lung transplantation. METHODS: Left lateral, orthotopic, allogeneic lung transplantation was performed between fully incompatible rat strains (Dark Agouti-->Lewis) after an average total ischemic time of 45 minutes. Group A (n = 6) served as control; no immunosuppression was used. In group B (n = 6), rats received 200 micrograms/kg/day SLX intravenously on days 0 to 4. The animals were killed on days 5 and 10, respectively. In groups C and D, syngeneic lung transplantation was performed (Lewis-->Lewis), with an ischemic time of 7 hours. Group C (n = 6) served as untreated controls. Group D rats (n = 6) received a single dose of 20 mg/kg SLX at the end of the ischemic time. The animals were killed on days 2 and 5, respectively. RESULTS: In group B rats, treated for rejection, a lower grade of rejection (2.7 +/- 0.6 vs 4.0 +/- 0.0, p < 0.05) and fewer infiltrating CD11a-positive leukocytes (6.6 +/- 2.7 vs 18.6 +/- 7.3, p < 0.05) were found histologically compared with group A. In group D rats, treated for reperfusion injury, a significant reduction of reperfusion injury was detected on chest radiograms and by histologic study. CONCLUSIONS: A synthetic oligosaccharide analog of SLX reduces allograft rejection and reperfusion injury by abrogation of P-selectin-dependent leukocyte-endothelial interaction. According to these findings, treatment with oligosaccharides to reduce reperfusion injury and rejection seems to be a promising strategy for clinical lung transplantation.

Animals↗
PubMed1996

Human thyroid epithelial cells cultured in monolayers. I. Decreased thyroglobulin and cAMP response to TSH in 12-week-old secondary and tertiary cultures.

An in vitro system of secondary and tertiary cultures of human thyroid epithelial cells (TFECs) in monolayer is described. The function of the cells was evaluated by the second messenger cAMP and the end product thyroglobulin (Tg). The Tg production from the cells was measured in the supernatant by a newly developed enzyme-linked immunosorbent assay. The TFECs in secondary monolayer cultures had preserved the ability to produce Tg and cAMP despite lack of polarization. Furthermore, a preserved ability of TSH-stimulated production of Tg and cAMP in 12-week-old secondary and tertiary cultures was found. However, the Tg and cAMP levels decreased gradually with the age of the cultures. In the secondary culture the TSH-stimulated Tg production decreased from 253 ng/micrograms DNA (205-263) after 3 weeks to 18 ng/micrograms DNA (6-81), P < 0.001, n = 6 after 12 weeks and TSH-stimulated cAMP production from 660 pmol/micrograms DNA (500-840) to 60 (40-200), P < 0.001, n = 6. The decreased responsiveness of long-term cultures results in preference of short-term secondary cultures, which provide a more suitable experimental model for in vitro investigation of human thyroid cell functions.

Cells, Cultured↗
PubMed1996

Human thyroid epithelial cells cultured in monolayers. II. Influence of serum on thyroglobulin and cAMP production.

An in vitro system of secondary cultures of human thyroid follicular epithelial cells in monolayer is described. The 72-h influence of serum and six supplements (thyrotropin, insulin, somatostatin, transferrin, hydrocortisone, glycyl-histidyl-lysine acetate) on growth and function in presence of 3-isobutyl-L-methyl-xanthine (IBMX) was investigated. The function of the cells was evaluated by production of the second messenger adenylate cyclase (cAMP) and the end product thyroglobulin (Tg). Growth was measured as the 3H-thymidine uptake of the cells. Three days of TSH-depletion preceeded the experiments. In presence of IBMX TSH stimulated cAMP production, while stimulation of Tg was only present in some cultures. In absence of IBMX TSH always stimulated the Tg production. The stimulation was independent of the presence of the other five investigated nutritional factors in physiological concentrations. TSH in concentrations from 0.1-10 U/1 stimulated the 72ih 3H-thymidine uptake of the cells. The TSH-stimulated production of Tg and cAMP decreased significantly with increasing concentrations of fetal calf serum (0-10%), (tau = 0.49, P < 0.001, n = 6-29 and tau = 0.75, P < 0.001, n = 6-29, respectively). Thus, serum as a complex, variable and not fully characterized mixture of hormones and growth factors was crucial to the attachment of the cells to the substrate, but inhibited differentiated functions of the human thyroid cells.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Therapy for lung failure using nitric oxide inhalation and surfactant replacement.

Nitric oxide inhalation and surfactant replacement therapy are relatively new concepts in the treatment of respiratory failure due to hypoxia and reperfusion injury after lung transplantation. We report on a patient in whom reperfusion injury of the lung developed after resuscitation and implantation of a biventricular assist device for sudden cardiac arrest. Lung failure developed within 12 hours after implantation of the biventricular assist device. Lung function was reestablished using combined therapy of nitric oxide and surfactant. Heart transplantation was performed successfully thereafter. This case indicates the potential role of a combined therapy of nitric oxide and surfactant in acute hypoxic lung failure.

Adult↗
PubMed1996

3-Carboxy-20-keto steroids are dual uncompetitive inhibitors of human steroid 5 alpha-reductase types 1 and 2.

Steroidal 3-carboxy-20-ketones have been prepared within two structural series, the androsta-3,5-dienes and the estra-1,3,5-trienes, as potential inhibitors of types 1 and 2 steroid 5 alpha-reductase, the enzyme activity responsible for the final step in biosynthesis of dihydrotestosterone. These compounds are shown to be potent uncompetitive inhibitors of both human recombinant enzyme activities, defining a novel class of dual steroid 5 alpha-reductase inhibitors.

5-alpha Reductase Inhibitors↗
PubMed1996

Thoracoscopic creation of a pericardial window for recurrent pericardial effusion after heart transplantation.

A 56-year-old man underwent orthotopic heart transplantation (Htx) for dilative cardiomyopathy. The postoperative course was uneventful despite the appearance of pericardial effusions during the first 6 months, which required repeated drainage therapy. Six months postoperatively a pericardial window was created using a thoracoscopic approach via the right pleural cavity. The course after this intervention was uncomplicated and there was no recurrence of the pericardial effusion during 18 months of follow-up.

Endoscopy↗
PubMed1996

Early postoperative flow rates after internal thoracic artery grafting for the left coronary artery system.

OBJECTIVE: The low perioperative flow rates of internal thoracic artery (ITA) conduits have been regarded as a limitation of their use in critical coronary situations with a high myocardial blood demand. To clarify whether these restrictions are justified, early postoperative flow rates were determined. METHODS: Following bilateral ITA grafting, 48 of 106 patients (April 1993-September 1994) underwent recatheterization. Subsequent to control angiography between days 8 and 12, 20 of these patients were studied by intravascular Doppler techniques applied for ITA grafts supplying the left anterior descending artery (LAD) and branches of the circumflex system (CX) (n = 20). Doppler spectral analysis allowed for determination of the average peak velocity and diastolic-systolic velocity ratio. Vascular diameters were assessed by simultaneously performed quantitative angiography and mean flow rates were calculated. All parameters were recorded at rest and following selective stimulation with nitroglycerin (0.2 mg) and papaverine (12.5 mg) to evaluate the graft flow capacity. RESULTS: Baseline values of average peak velocity at rest were 24.6 +/- 11.5 cm/s for ITA-LAD conduits and 21.9 +/- 6.8 cm/s for ITA-CX pedicles. Following dilative stimulation with papaverine, a significant increase in average peak velocities were obtained for both locations (ITA-LAD: 47.3 +/- 17.1 cm/s, ITA-CX: 42.3 +/- 11.8 cm/s). The application of nitroglycerin had a similar effect (ITA-LAD: 42.6 +/- 15.3 cm/s, ITA-CX: 40.3 +/- 10.7 cm/s). The vascular diameters of ITA conduits remained unchanged on nitroglycerin stimulation, whereas papaverine effected significant dilatation in both locations. Flow rates at rest were not significantly different (ITA-LAD: 51.0 +/- 34.2 ml/min, ITA-CX: 44.7 +/- 16.4 ml/min) and maximal flow increase was observed following papaverine stimulation of the LAD conduits (116.1 +/- 90.6 ml/min). Dilative stimulation effected an increase in diastolic-systolic velocity ratios from average values at rest in a range between 34% and 41.7% for both groups and substances. CONCLUSIONS: The basic blood flow in functioning ITA grafts appears to be similar in conduits supplying the LAD and marginal branches. Flow rates between 50 and 60 ml/min at rest should meet myocardial demands, even in the LAD position. Increased flow rates were predominantly based on higher flow velocities with an increased diastolic flow proportion. Enlargement of the graft diameter may exert additional effects, at least following papaverine stimulation at a particular concentration.

Blood Flow Velocity↗
PubMed1996

Do long-term results justify bridging to heart transplantation in patients with multi-organ dysfunction?

This retrospective study was performed to determine the influence of multi-organ dysfunction and the type of preoperative hemodynamic support on mortality after heart transplantation. All patients undergoing heart transplantation during a 6 year period were divided into 3 groups: group A patients (n = 110) had stable hemodynamics on oral medication, group B recipients (n = 41) received continuous i.v. catecholamine application, and in group C (n = 21) mechanical hemodynamic support was necessary. In groups B and C elevated serum creatinine and transaminase levels-reflecting renal and hepatic dysfunction-were detected more often and the survival rate was worse during the first six months (A: 85%, B: 71%, C: 52%, p < 0.01). In group C the prognosis of patients with multi-organ dysfunction was significantly worse compared to patients with normal renal and hepatic function (38% vs. 75%; p < 0.01). In recipients surviving for six months, there was no difference in long-term prognosis between the groups studied. It is concluded that heart transplantation in patients with multi-organ dysfunction on invasive hemodynamic support bears a significantly increased risk in the early postoperative period. In view of the current donor shortage the condition of other organs should be improved before transplantation as far as possible, even using long-term mechanical support.

Adult↗
PubMed1996

Ectopic production of intact parathyroid hormone by a squamous cell lung carcinoma in vivo and in vitro.

Ectopic tumoral production of intact parathyroid hormone (PTH) is rare. The PTH-related protein is the common cause of hypercalcemia in most solid tumors, particularly squamous and renal carcinomas. We report the case of a 71-yr-old man with a PTH-producing squamous cell lung carcinoma. Immunocytochemical analysis of the tumor tissue as well as of cultured tumor cells revealed PTH positive staining. Cultured tumor cells released PTH and were calcium sensitive, producing 122 +/- 16 pg/microgram DNA of intact PTH (mean +/- SEM) at 0.5 mmol/L calcium compared with 26 +/- 2 pg/microgram DNA at 3.0 mmol/L calcium. Somatostatin analogues have been used in the treatment of humoral hypercalcemia of malignancy (HHM). However, we found that somatostatin (0.1 microgram/L) in cultured tumor cells increased the release of intact PTH (123 +/- 19 versus 82 +/- 1 pg/microgram DNA, P < 0.05) and thus might have a negative effect on the HHM. This report is the first to describe a true ectopic PTH-producing squamous cell lung carcinoma associated with HHM.

Aged↗
PubMed1996

[Coronary heart disease and impaired left ventricular function in patients over 80 years of age--is bypass operation justified?].

Between April 1988 and February 1995, 35 patients aged 80 years or older underwent elective coronary artery bypass grafting. Concomitant aortic valve replacement was performed in eight patients. Fifteen patients with moderate to severe left ventricular dysfunction (left ventricular ejection fraction (EF) 20 to 45%) (group I) were compared to 20 patients with an EF > 45% (group II). There were no differences according to age, NYHA classification and associated diseases. Group I patients had significantly more myocardial infarctions compared to group II (1.3 +/- 1.1 vs. 0.5 +/- 0.8; p < 0.05). Also more bypass grafts per patient were used in group I (3.1 +/- 0.9 vs. 2.3 +/- 0.9; p < 0.01). No differences between the groups were observed in the postoperative course. One patient of group II died from multiorgan failure (hospital mortality 2.2%). A follow-up could be performed in 32 of 34 hospital survivors (94%) 12.0 +/- 11.2 months (1-41 months) postoperatively. There was one non-cardiac death in each group. All hospital survivors improved by at least one NYHA functional class. Actuarial survival at 3 years is 91% in both groups. In patients aged 80 years or older with or without left ventricular dysfunction coronary artery bypass surgery can be performed with an acceptable risk and a functional benefit. Thus, elective operations should be performed in this age group despite left ventricular dysfunction.

Aged↗
PubMed1996

[Is heart surgery in over 80-year-old patients justified?].

Coronary artery bypass grafting and/or aortic valve replacement was performed in 68 patients aged 80 or older. These patients were compared to 743 patients younger than 80 years. In octogenerians cardiac surgery can be performed with an acceptable risk and a functional benefit.

Aged↗
PubMed1996

[Simultaneous operations of the carotid bifurcation and coronary vessels in moderate systemic hypothermia].

Comorbidity of coronary heart disease and carotid stenosis raises the question of surgical stratification. A simultaneous approach of carotid endarterectomy and coronary revascularization, both under conditions of moderate hypothermic extracorporeal circulation, was applied in 48 patients. Considering the complexity of the procedures required the 30-day mortality (2.1%) and perioperative incidence of permanent stroke (2.1%) or myocardial infarction (0%) appeared to be comparably low.

Aged↗
PubMed1995

Thoracoscopic pericardial fenestration after cardiac transplantation.

A patient suffered from recurrent pericardial effusions following heart transplantation. Repeated pericardiocentesis and insertion of pericardial drains could not resolve the problem and therefore surgical intervention was necessary. The procedure was performed as a minimally invasive thoracoscopic pericardial fenestration. Four months postoperative the patient was without recurrences. This method of pericardial fenestration after heart transplantation has been used for the first time.

Heart Transplantation↗
PubMed1995

Cloning, expression and functional characterization of type 1 and type 2 steroid 5 alpha-reductases from Cynomolgus monkey: comparisons with human and rat isoenzymes.

The Cynomolgus monkey may provide an alternative pharmacological model in which to evaluate the efficacy of novel inhibitors of the two known human steroid 5 alpha-reductase (SR) isoenzymes. To evaluate the suitability of this species at the level of the molecular targets, a Cynomolgus monkey prostate cDNA library was prepared and screened using human SR type 1 and 2 cDNAs as hybridization probes. Two distinct cDNA sequences were isolated encoding the monkey type 1 and 2 SR isoenzymes. These sequences share 93 and 95% amino acid sequence identity with their human enzyme counterparts, respectively. Difference in monkey type 1 SR, however, was found within the contiguous four amino acids corresponding to the regions in the human and rat sequences that have been proposed previously to influence steroid and inhibitor affinities. Subsequently, both monkey cDNAs were individually expressed in a mammalian cell (CHO) line. Enzyme activities of both monkey SRs were localized to the membrane fractions of CHO cell extracts. Like the human and rat enzymes, the monkey type 1 and type 2 SRs were most active at neutral and low pH, respectively. The results of inhibition studies with over 30 known SR inhibitors, including epristeride, 4MA, and finasteride, indicate that the monkey SR isoenzymes are functionally more similar to the human than the rat homologues. The results from initial velocity and inhibition studies as functions of pH with the human and monkey type 2 SRs also compare favorably. These results, together, suggest that the monkey SR isoenzymes are structurally and functionally comparable on a molecular level to their respective human counterparts, supporting the relevance and use of the Cynomolgus monkey as a pharmacological model for in vivo evaluation of SR inhibitors.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

Comparative digestion in cattle and sheep fed wheat silage diets at low and high intakes.

Winter wheat (Triticum aestivum L.), harvested at late milk, early dough, and hard dough stages of maturity was ensiled for nutritive comparisons. Diets were adjusted to 13% CP with a soy protein concentrate and fed to six ruminally fistulated growing steers and nine adult wethers in a repeated 3 x 3 Latin square design to study the effects of maintenance and ad libitum intakes on digestibility of different feed fractions. At both intakes, digestion values for the steers were greater than or equal to those for the sheep for all feed fractions except CP. Wethers achieved greater intake per unit of BW than steers during ad libitum intake. Voluntary OM intakes of steers only differed between the milk stage diet and the dough stage diets. At low intake, the diets containing the more mature silage were more digestible. At high intake, the OM of diet containing the early dough stage silage ws most digestible. Increased intake caused a depression in digestibility of different feed fractions. The magnitude of the depression varied among diets and fractions. Data indicated that the nutritive value of diets based on whole crop wheat silage is affected by stage of maturity, animal species, and amount of intake. The assessment of the nutritive value of diets based on whole crop wheat silage should therefore be made with the animal species and at the amount of intake for which the diets are intended.

Animals↗