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Biomedical subjects

N Franke

Publications and source records attributed to N Franke.

At least 19 recordsLinked to original sources
PubMed2004

Autologous stem cell transplantation in primary systemic amyloidosis: the impact of selection criteria on outcome.

Autologous stem cell transplantation (ASCT) for primary systemic amyloidosis (AL) produces high hematologic and organ responses. However, treatment-related mortality remains high and reported series are subject to selection bias. In all, 48 of 80 amyloid patients referred to our center had AL in the absence of myeloma, 26 of these 48 were deemed transplant candidates and 20 actually underwent ASCT. Transplant-related mortality has fallen from 50 to 20% since January 1999 due to better patient selection and prophylactic measures. Intent-to-treat organ responses were renal (46%), cardiac (25%) and liver (50%). Organ responses in patients who survived transplantation were renal (75%), cardiac (40%) and liver (100%). The 3-year OS post-ASCT was 56% with improved outcome predicted by a better performance status (P=0.08), normal ALP (P=0.08), nephrotic syndrome (P=0.01) and the absence of severe hypotension (P=0.01). The 3-year OS for all referred patients was 44% and this was not significantly better for transplant candidates. Patients with significant hypotension (systolic blood pressure < or =90 mmHg) or poor performance status (ECOG >2) have an exceedingly high treatment-related mortality and should not be transplanted. For those undergoing ASCT, organ response rates appear promising, but conclusive evidence of improved survival for this select group of patients is still lacking and will require randomized trials.

Adult↗
PubMed2002

Sequential changes in compliance and resistance after bolus administration or slow infusion of surfactant in preterm infants.

OBJECTIVE: As bolus instillation of surfactant can lead to acute pulmonary, hemodynamic and cerebral side effects, we tested whether pulmonary mechanics and gas exchange differ between slow surfactant infusion and bolus administration. DESIGN AND SETTING: Prospective, randomized pilot study in a tertiary care university hospital. PATIENTS AND METHODS: Of 20 consecutive preterm infants (27-35 weeks' gestation) with severe respiratory distress syndrome) who were enrolled 14 with bovine surfactant finally were analyzed. INTERVENTIONS: Six treatments were administered by slow endotracheal surfactant infusion and eight as a bolus. Static compliance (C(stat)) and resistance (R(rs)) were measured every 3 min. RESULTS: C(stat) first decreased and then increased in both groups. In the infusion group C(stat) after 90 min was significantly higher than after bolus treatment but not after 15 or 45 min. R(rs) increased about threefold, with large fluctuations in the bolus group. After 90 min PaO(2)/FIO(2) had increased from 111+/-44 to 254+/-69 in the bolus group and from 86+/-40 to 238+/-102 in the infusion group, but early FIO(2) reduction and increase in PaO(2)/FIO(2) seemed delayed in the infusion group. CONCLUSIONS: Very slow infusion of natural surfactant is at least as effective as bolus instillation in terms of improvement in C(stat) and oxygenation after 90 min. However, until 90 min the course of C(stat) and indices of gas exchange seem superior after bolus therapy. Because R(rs) is substantially increased, long expiratory times are required to yield complete exhalation.

Airway Resistance↗
PubMed2000

Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy.

Limb girdle muscular dystrophy is a group of clinically and genetically heterogeneous disorders inherited in an autosomal recessive or dominant mode. Caveolin-3, the muscle-specific member of the caveolin gene family, is implicated in the pathogenesis of autosomal dominant limb girdle muscular dystrophy 1C. Here we report on a 4-year-old girl presenting with myalgia and muscle cramps due to a caveolin-3 deficiency in her dystrophic skeletal muscle as a result of a heterozygous 136G-->A substitution in the caveolin-3 gene. The novel sporadic missense mutation in the caveolin signature sequence of the caveolin-3 gene changes an alanine to a threonine (A46T) and prevents the localization of caveolin-3 to the plasma membrane in a dominant negative fashion. Caveolin-3 has been suggested to interact with the dystrophin-glycoprotein complex, which in striated muscle fibers links the cytoskeleton to the extracellular matrix and with neuronal nitric oxide synthase. Similar to dystrophin-deficient Duchenne muscular dystrophy, a secondary decrease in neuronal nitric oxide synthase and alpha-dystroglycan expression was detected in the caveolin-3-deficient patient. These results implicate an important function of the caveolin signature sequence and common mechanisms in the pathogenesis of dystrophin-glycoprotein complex-associated muscular dystrophies with caveolin-3-deficient limb girdle muscular dystrophy.

Amino Acid Substitution↗
PubMed1990

Selective alterations in natural killer cell subsets in patients with atopic dermatitis.

We examined the immunophenotypic characteristics of natural killer (NK) cell subsets in patients with severe atopic dermatitis (AD), rhinitis allergica (RA) and in healthy controls. Expression of CD16, CD56 and CD57 antigens on peripheral blood lymphocytes was evaluated by simultaneous double immunocytofluorometry. Our results showed significantly lower percentages of cells with CD16, CD56 and CD57 surface antigens in patients with AD. Furthermore subdivision of the AD group into two subgroups, AD1 and AD0 (with and without antigen-specific IgE antibodies against potent inhalative allergens, i.e. mite, grass, rye, birch, cat) revealed that patients of subgroup AD1 showed a more prominent decrease compared to that of subgroup AD0. Moreover, we found a significant negative correlation between the percentage of CD56 + CD16 + NK cells and total IgE levels in serum, which were significantly higher in patients of subgroup AD1 than in AD0. NK cell activity was deficient in patients with AD but there was no difference between both subgroups. These data indicate that considerable heterogeneity in immunologic regulation may exist in patients with AD with regard to their NK cell subsets.

Adult↗
PubMed1989

Combined therapy of xenografts of human pancreatic carcinomas with rTNF-alpha and mitomycin C.

Based on previously published experimental studies in nude mice indicating that rTNF-alpha as well as mitomycin C are able to induce significant growth inhibition of xenotransplants of gastrointestinal and pancreatic carcinomas we have investigated the antitumor effects of rTNF-alpha (0.8 mg/kg daily for 21 days) and mitomycin C (2.4 mg/kg once weekly, day 1, 7, 14) as single drugs and in combination (0.8 + 2.4) in nude mice bearing xenografts of 4 human pancreatic carcinomas and 1 colorectal cancer. Serum CA 19-9 was measured additionally to tumor growth rate. The results demonstrate that combined treatment is more effective compared to rTNF-alpha and mitomycin C alone. Combined therapy resulted in a significant inhibition of tumor growth in 3 of 5 xenografts and in decrease of tumor volume to less than 50% of the initial values in 2 of 5 tumors. The results support the concept that combinations of cytokines with cytostatics might be of value for treatment of gastrointestinal and pancreatic cancer in vivo.

Animals↗
PubMed1989

Cytokines and pancreatic cancer. Sensitivity of xenotransplants of predominantly pancreatic carcinomas to rIFN-gamma and rTFN-alpha in nude mice.

Ten xenotransplants of human gastrointestinal carcinomas (eight human pancreatic carcinomas) were assayed for their sensitivity to human rIFN-gamma and human rTNF-alpha in nude mice. Both substances demonstrated a dose and route dependent antitumoral activity in principle. However, the extent of response varied distinctly between the tested xenografts. rTNF-alpha was clearly superior to rIFN-gamma at systemic application of comparable doses (0.8 mg/kg/d). Intramural administration of both cytokines could cause cytotoxic effects and was significantly more effective than systemic administration that predominantly resulted in antiproliferation. Growth inhibition of rIFN-gamma or rTNF-alpha alone could be clearly enhanced by combining both cytokines. In addition, the results suggest: the possibility to enhance the effects of rIFN-gamma alone also by combination with nIL 2, as well as a decrease of the effects of rTNF-alpha with time of therapy.

Animals↗
PubMed1988

Pulmonary kinetics of fentanyl and alfentanil in surgical patients.

The pulmonary kinetics of fentanyl and alfentanil were studied quantitatively in two groups of five and six surgical patients, respectively, after the induction of anaesthesia. A mixture of one of the opioids and indocyanine green was administered as a bolus. From measurements of the concentrations of the dye in plasma and the opioids in blood, central blood volume and the amount of drug which passed through the pulmonary circulation were calculated. The pulmonary release of fentanyl and alfentanil was calculated from the arterial-mixed venous blood concentration differences. Fentanyl 43.0-86.9% (median 70.9%) and 35.9-79.8% of alfentanil (median 58.6%) were sequestered by the lung on first passage of the opioid-containing blood through the pulmonary capillaries. During the following 14 min, fentanyl was released, apparently from two binding sites (T1/2fast: 0.22 (0.16-0.27) min; T1/2slow: 5.78 (3.65-13.86) min). Initially, there was a rapid release of alfentanil (T1/2: 0.28 (0.08-0.51) min). However, 1-3 min after injection, the arterial-mixed venous blood concentration differences of alfentanil disappeared, although considerable amounts of drug were still present in the lung of five of the six patients studied. It may be expected that a temporary pulmonary sequestration of fentanyl and alfentanil has considerable impact on the time course of their pharmacological effects, on the time necessary to reach their maximum effect and on the intensity and (in case of fentanyl) the duration of these effects.

Adult↗
PubMed1988

[The computer as an aid in attention training--a clinico-experimental study].

Reported is the evaluation of a computer-directed training programme for visual attention, that is based on the results of experimental studies by Zubin (1975) and Shakow (1979). With reference to Zubin's model, this training programme addresses active maintenance of selective visual attention (in terms of "sustained attention"), applying Shakow's diagnostic research paradigm (with a preparatory stimulus, an RT stimulus, and a variable preparatory interval) in a behavioural setting (learning of strategies for attention) for clinical purposes. In a pre-post-study carried out for a three-week programme, the results of single case experiments showed a significant decrease of reaction time variability, which partly persisted in follow-up studies. It was found that attentional performance increased in both psychotic patients and patients with cerebral dysfunction. In the second phase of statistical validation on patients with psychotic attention deviations, both attention performance and transfer effects were verified. The behavioural training methods, which were implemented to foster attention, proved helpful in the majority of cases. For greater practicability, a programme version for use on the home computer has been developed. The study on the whole illustrates the growing utilization of computer technology in neuropsychological rehabilitation.

Adult↗
PubMed1987

Induced hypotension: action of sodium nitroprusside and nitroglycerin on the microcirculation. A micropuncture investigation.

Sodium nitroprusside (SNP)-induced hypotension is associated with tissue hypoxia in liver and skeletal muscle, suggesting a redistribution of nutritional capillary flow. To test this hypothesis, the effects of SNP and nitroglycerin (NTG) on striated muscle vessels were studied in 42 hamsters using intravital microscopy, quantitative video image analysis, a platinum multiwire electrode for local Po2 measurements, and a micropuncture system for the determination of microcirculatory pressure. A transparent chamber was implanted in a dorsal skin fold. When the mean arterial pressure was reduced to 70 or 40 mmHg by SNP, the precapillaries dilated and precapillary resistance decreased, but significant changes in venular diameter were not observed. However, SNP-induced hypotension was associated with a consistent increase in intravascular pressure within the venules. As a result, the arteriolar-venular pressure gradient was reduced by more than 50%. Furthermore, the functional capillary density was less, and tissue hypoxia was present during SNP hypotension. In contrast, NTG dilated both arterioles and venules in the microvascular network. Despite a lower blood cell velocity in all segments, the functional capillary density and local Po2 remained unchanged during NTG, principally because there was only a 10% reduction of the arteriolar-venular pressure gradient. These findings suggest that, in terms of tissue oxygenation, NTG may be preferable to SNP for deliberate hypotension.

Animals↗
PubMed1983

Total and ionized calcium levels during open heart surgery with two different pump priming solutions.

UNLABELLED: Changes of total (Ca) and ionized Ca-levels (Ca2+) were studied during open heart surgery in 18 patients. 9 patients (group A) had only crystalloid solutions as pump priming, the other 9 patients (group B) had 500 ml of citrated whole blood in the priming solution. For assessment of hemodilution hct and total plasma protein and plasma albumin were determined. Measurements were done preoperatively, before and after systemic heparinisation, during and after extracorporeal circulation (ECC) and on the first postoperative day. RESULTS: 1. Anticoagulation with 375 U/kg BW heparin had no effect on ionized calcium levels. 2. With onset of ECC (Ca) decreased by 30% in group A and by 20% in group B. (Ca2+), however, decreased by 20% in group A and by 35% in group B. The percentage of ionized calcium increased by 15% in group A whereas it decreased by the same amount in group B. This difference is contributed to the calcium binding effect of citrate added to pump priming in group B. Mechanisms of the relative increase of ionized calcium during ECC in group A, however, remain to be studied.

Blood Glucose↗
PubMed1983

[Effects of halothane and enflurane on the microcirculation].

The microcirculatory effects of halothane and enflurane were studied in a new experimental model before, during and after anaesthesia. It was only with complete volume substitution and a constant CVP during anaesthesia that blood cell velocity and capillary perfusion remained unchanged, whereas functional capillary density shifted the histogram of local pO2 to the right, i.e. towards increased pO2 values. Spontaneous arteriolar vasomotion was inhibited during anaesthesia with halothane and enflurane. The study also shows that homogeneous capillary perfusion and microcirculatory flow distribution during anaesthesia are closely related to normovolaemia and changes in CVP.

Anesthesia↗
PubMed1982

[Report on a successful orthotopic cardiac transplantation in Germany].

The first successful heart-transplantation carried out in the Department for Cardiovascular Surgery of the University of Munich, Klinikum Grosshadern is reported. The recipient, 32 years old at the time of operation, had sustained a large antero-lateral-septal myocardial infarction in June 1980; thereafter the left ventricular ejection fraction was severely impaired (e.f. = 19%). Yet, the operation was definitely planned some year later, after the patient had survived an embolus to the right lung, an acute left heart failure and a small ulcer of the stomach. The operation was performed on 8-19-1981. The donor was a 23 year old young man, who had met a fatal motorcycle accident 10 days ago. The man was pronounced dead in the afternoon of the preoperative day according to the criterions of the German Society for Surgery by means of a carotid angiogram. Donor and recipient were well matched in regard to blood group, HLA-A2-System and finally cross-match-test. Transplantation was carried out according to the technique of Lower and Shumway. Immediately p.o., immunosuppressive therapy was started using azathioprine, cortisone and antihuman thymocyte globulin. Two acute rejections were noted, the first from p.o. day 6 to 15, the second from p.o. day 22 to 34. The second acute rejection was complicated by a pneumatosis cystoides intestinii, which caused a change of the immunosuppressive therapy to Cyclosporin A. No further complications were registered in the following p.o. course, the patient is discharged since Christmas 1981.

Adrenal Cortex Hormones↗
PubMed1982

[Effect of the intravenous administration of lormetazepam on hemodynamics and arterial blood gases in patients with coronary heart disease].

In 11 conscious patients suffering from coronary artery disease undergoing aorto-coronary bypass operations the hemodynamic and respiratory effects of Lormetazepam were investigated preoperatively. Lormetazepam was administered i.v. in a dosis of 2 mg (average weight 70.4 +/- 5.7 kg) into the right atrium. The maximum of hemodynamic changes was found about 10 min after injection. At that time the mean arterial pressure was diminished about 14%. At the same time total peripheral resistance fell about 15% below the control level. The cardiac index remained unchanged. The hemodynamic effect therefore consisted in a peripheral vasodilation. This was emphasized by the reduction of right atrial pressure and pulmonary capillary wedge pressure. The heart rate was unchanged. The arterial pO2 was reduced to 18% below the control level. The arterial pCO2 was increased about 24%. This finding is possibly due to an additional effect of Morphine and Phenobarbital used for premedication.

Anti-Anxiety Agents↗