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Biomedical subjects

K Pfeiffer

Publications and source records attributed to K Pfeiffer.

At least 37 records · Page 2Linked to original sources

Human diseases with defects in oxidative phosphorylation. 1. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies.

The amount of oxidative phosphorylation enzymes in mitochondrial encephalomyopathy patients has been studied by two-dimensional electrophoresis (blue native PAGE/Tricine-SDS-PAGE). Only 20 mg muscle was required to identify and analyse complexes I, III, IV, and V after Coomassie staining. In most cases reduced amounts of the involved complex(es) correlated well with decreased enzyme activities. The reliability of the method was reflected by the constant mutual ratio of the complexes found in all controls. Deviations from normal ratios were found to be more sensitive indicators for a defect than the absolute quantities, which varied considerably within the control group both in the enzymic and in the electrophoretic analysis. The effect of the mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes on the amount of oxidative phosphorylation complexes was demonstrated for the first time directly on the protein level. In patients without known DNA mutations, specific defects of single complexes were identified. The new technique is a sensitive method for the identification of oxidative phosphorylation defects, complementary to enzymic measurements.

Adult↗

HLA-DP antibodies in patients awaiting renal transplantation.

Sera from 505 patients awaiting renal transplantation with known panel-reactive cytotoxic antibody (PRA) status were tested for HLA-DP antibodies of the IgG class by means of the monoclonal antibody immobilization of leukocyte antigens (MAILA) technique. The overall incidence of HLA-DP antibodies was 7.3%. A positive HLA-DP antibody status correlated only weakly (r = 0.23) with a positive cytotoxic antibody status. After retrospective analysis, patients with HLA-DP antibodies prior to retransplantation revealed a significantly (P < 0.025) higher graft function rate than HLA-DP-negative patients. One patient was found to possess IgG HLA-DP autoantibodies prior to transplantation; thus far, his graft has been functioning for more than 2 years.

Antibodies↗

[Inadvertant suture fixation of a Swan-Ganz catheter to the pulmonary artery following heart surgery].

We report a patient undergoing redo cardiac surgery for combined replacement of the aortic and mitral valves. During the course of the operation, a Swan-Ganz catheter - positioned preoperatively - was accidentally fixed to the wall of the pulmonary artery. As this did not interfere with cardiac output measurement or the pulmonary artery pressure wave form, the fixation was not noticed until an attempt was made to remove the catheter. Fluoroscopy revealed both the catheter's immobility and the location of the suture fixation. The patient required a sternotomy to remove the catheter. In order to avoid this complication, the indications for pulmonary artery catheters during cardiac surgery should be carefully considered. If catheters are inserted, their mobility should by all means be ensured before the chest is closed.

Aged↗

Stress experienced while travelling without sight.

The purpose of this study was to examine the stress reaction of pedestrians travelling without sight and the stress-reducing effect of a relaxation exercise immediately following travel. 16 students in special education volunteered for this experiment. They were blindfolded while travelling. A trait-state-anxiety questionnaire was administered. Analysis of variance indicated statistically significant effects. Travelling without sight increased state-anxiety as compared to trait-anxiety. With a simple relaxation technique, state-anxiety was reduced appreciably.

Adult↗

[Diagnostic and therapeutic measures in craniocerebral trauma in the intensive care unit].

Diagnostic and therapeutic measures after severe head-injury in the intensive care unit are discussed. The main goal of all efforts consists in minimizing secondary brain damage. Adequate shock therapy in the initial phase proves crucial for the later outcome. Methods and indications of intracranial pressure monitoring are described. Electrophysiological tests, transcranial doppler sonography, EEG and serial CCT controls provide valuable additional information. Frequent clinical assessments however remain the golden standard despite all technical advances. Surgical and conservative modalities of therapy are further examined. Controversial methods (barbiturates, steroids, some osmotic active agents) as well as new concepts of therapy are also included. The clinician is provided with a critical discussion of the value of the different methods from our point of experience.

Brain Damage, Chronic↗

Angiotensin blockade or calcium antagonists improve endothelial dysfunction in hypertension: studies in perfused mesenteric resistance arteries.

Endothelial regulation of peripheral vascular resistance is impaired in hypertension. We studied the effects of different antihypertensive therapies on endothelial function in perfused mesenteric resistance arteries. Spontaneously hypertensive rats (SHR) aged 7 weeks were treated with either the nonpeptidic angiotensin II (AII) receptor antagonist CGP 48369, the angiotensin-converting enzyme (ACE) inhibitor benazepril HCl, or the calcium antagonist nifedipine (each 10 mg/kg/day orally, p.o.) for 8 weeks. All forms of therapy inhibited the increase in systolic blood pressure (SBP) to a comparable degree (18-23 mm Hg) and reduced but did not normalize medial hypertrophy in SHR. Changes in intraluminal vascular diameter to acetylcholine (ACh), norepinephrine (NE), and endothelin-1 (ET-1) were measured. Impaired endothelium-dependent relaxations to intraluminal ACh improved or normalized with all therapies, whereas the response to extraluminal ACh (which was unimpaired in SHR) remained unaffected. The endothelium-dependent inhibition of contractions to NE was lost in untreated SHR and improved or restored by antihypertensive therapy. In SHR, the sensitivity but not the maximal response of vascular smooth muscle (VSM) to ET-1 was paradoxically decreased. Antihypertensive therapy with CGP 48369, nifedipine, or benazepril HCl restored or increased the sensitivity to ET-1. Thus, chronic blockade of the renin-angiotensin system or voltage-operated calcium channels reduces BP and improves endothelial dysfunction in the resistance circulation of SHR. This may contribute to normalization of peripheral vascular resistance during antihypertensive treatment and improve local blood flow to vital organs.

Acetylcholine↗

Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.

BACKGROUND: Coronary artery disease is an important complication of hypertension. Therefore, the effects of antihypertensive therapy on the endothelial nitric oxide (NO)/L-arginine pathway and vascular smooth muscle were studied in left anterior descending coronary arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Angiotensin II (AT1) receptor antagonists CGP 48369 and valsartan, angiotensin-converting enzyme inhibitor benazepril HCl, and calcium antagonist nifedipine were used as antihypertensive agents. METHODS AND RESULTS: Rings were examined in myograph systems for isometric tension recording. In untreated WKY and SHR rings, acetylcholine (10(-9) to 10(-5) mol/L) but not bradykinin, substance P (both 10(-6) mol/L), or thrombin (1 U/mL) induced comparable endothelium-dependent relaxations. These relaxations were markedly decreased by NG-monomethyl-L-arginine (10(-4) mol/L) and fully prevented by N omega-nitro-L-arginine methyl ester (10(-4) mol/L) or methylene blue (10(-5) mol/L). In vitro treatment of WKY and SHR rings with benazeprilat, CGP 48369, or valsartan (3 x 10(-7) mol/L) did not affect responses to acetylcholine. In SHR, chronic therapy for 8 weeks with benazepril HCl, CGP 48369, valsartan, or nifedipine (each 10 mg.kg-1.d-1 PO) similarly reduced blood pressure and increased endothelium-dependent relaxations to acetylcholine (log shift at IC50, ie, half-maximal inhibition of a preceding contraction, 10-, 8-, 13-, and 13-fold, P < .05 versus control), whereas relaxations to the NO donor 3-morpholino sydnonimine (SIN-1, 10(-9) to 10(-5) mol/L) remained unaffected. In WKY, chronic therapy with nifedipine (10 mg.kg-1.d-1 PO) affected neither blood pressure nor relaxations to acetylcholine or SIN-1. CONCLUSIONS: In rat coronary arteries, NO is synthesized via the endothelial L-arginine pathway and released after stimulation with acetylcholine. In SHR, chronic antihypertensive therapy with either angiotensin receptor antagonists, an angiotensin-converting enzyme inhibitor, or a calcium antagonist specifically increased the normal endothelium-dependent relaxations to acetylcholine, probably because of their blood pressure-lowering effects, whereas the responsiveness of vascular smooth muscle to NO remained unaffected.

Angiotensin Receptor Antagonists↗

Prednimustine combined with mitoxantrone and 5-fluorouracil for first and second-line chemotherapy in advanced breast cancer.

A total of 60 patients with advanced breast cancer were treated with a combination of prednimustine (P: 110 mg/m2, days 1-5), mitoxantrone (M: 12 mg/m2, day 1) and 5-fluorouracil (F: 500 mg/m2, day 1) (PMF). Treatment was repeated every 3 weeks. In all 53 patients were evaluable for response. A total of 12 subjects had failed prior chemotherapy for metastatic disease. In response to PMF treatment we observed 21 partial remissions and 3 complete remissions, amounting to a total response rate of 45%. The median duration of response was 39 weeks, and median survival was 56 weeks. Dose-limiting side effects were leukopenia (40 cases) and thrombocytopenia (11 patients). Nausea and vomiting was experienced by 93% of subjects; in 56% of cases it reached WHO stage II-III. Alopecia occurred in 18% of our patients. Our results suggest that PMF represents an active regimen in the treatment of advanced breast cancer and yields a response rate of 45%. Considering that the majority of our patients had not received prior chemotherapy, the question remains open as to whether a 45% response rate outweighs the observed toxicity.

Adult↗

4'-O-tetrahydropyranyl-doxorubicin in advanced breast cancer: a phase II study.

In a phase II study, 35 patients with advanced breast cancer were treated with 4'-O-tetrahydropyranyl-doxorubicin (THP-DXR) (70 mg/m2 i.v. on day 1); treatment was repeated every 3 weeks. Eight patients had failed prior chemotherapy for advanced disease. A total of 34 patients were evaluable for response. After a median of 10 treatment courses (range, 3-15), objective tumor response was seen in 59% (20 of 34 patients) (95% confidence limits, 42%-75%). In all, 17 partial remissions and 3 complete remissions were observed; stable disease occurred in 13 patients. The median duration of response was 42+ weeks (range, 21 - 77+ weeks). The dose-limiting side effects were leukopenia (26 patients, WHO grade III-IV) and thrombocytopenia (9 patients, WHO grade II-IV). Nausea/vomiting was experienced by 34 patients; in 18, it reached WHO grade II-III. Other treatment-related side effects included alopecia (WHO grade II-III) in 26 patients and stomatitis and diarrhea (WHO grade I-III) in 9 patients. At cumulative doses of THP-DXR of at least 700 mg/m2 (range, 700-1,050 mg/m2), no signs of congestive heart failure were observed. We conclude that THP-DXR is effective for first- and second-line chemotherapy in advanced breast cancer and that side effects are manageable.

Adult↗

Ectopic bone induction by partially purified bone extract alone or attached to biomaterials.

Formation of new bone is suggested to be caused by interaction of a set of chemical factors with mesenchymal target cells. A specific assembly of factors, i.e. chemotaxis-, adhesion-, proliferation- and differentiation-factors, as well as macromolecular structure components, essential for formation of large amounts of ectopic bone was termed "osteopoetin" (OP). In the present study a partially purified osteopoetin containing bovine bone extract (OCBE) was used to induce ectopic bone formation. In order to reduce the amount of OCBE necessary for bone induction, OCBE was seeded onto different commercially available collagens or poly-L-lactic acids (PL). Solid collagens in a sponge-like form were used for the first time to function as an attachment system for an osteoinductive substance. The test substances were implanted into abdominal muscle pouches of male Wistar rats. After 21 days the implants were harvested and evaluated histologically. OCBE resulted in the formation of large ossicles containing hematopoietic bone marrow. The minimal amount of OCBE to elicit ectopic bone formation can be reduced by a factor of 10 when attached to quickly resorbable collagens, but not when attached to slowly resorbable PL. These results suggest that collagens are suitable OCBE attachment systems and useful for clinical application.

Animals↗

Is there any correlation between platelet aggregation, plasma lipoproteins, apoproteins and membrane fluidity of human blood platelets?

Fluorescence anisotropy (which is inversely related to membrane fluidity) of gel filtered platelets of 18 normolipemic subjects (20-26 years) was measured after incubation with three different fluorescent probes (DPH, TMA-DPH, and 6-As). These values were correlated to both platelet aggregation parameters after stimulation with ADP (4 microM), epinephrine (10 microM) or collagen (2 micrograms/ml PRP) and to plasma lipids, lipoproteins and apoproteins. Fluorescence anisotropy values after DPH-labeling of platelets were only negatively correlated to TG (p less than 0.05). No correlation was found between fluorescence anisotropy values of DPH, TMA-DPH and 6-As to LDL-C, Lp(a), HDL-C and HDL3-C (p less than 0.01). However, fluorescence anisotropy values of DPH and TMA-DPH were negatively correlated to apoproteins A2 and B (p less than 0.05). No correlations were found between fluorescence anisotropy after DPH labeling and different aggregation parameters. TMA-DPH and 6-As fluorescence anisotropy values are correlated to epinephrine induced stimulation (p less than 0.01).

Adult↗

Evaluation of fetal heart rate artifacts, hemodynamics and digoxin treatment in fetal tachyarrhythmia by Doppler measurement of fetal blood flow--case report of a pre-excitation syndrome.

A fetal cardiac arrhythmia may cause misleading fetal heart rate tracings with unreliable signs of fetal distress. Assessment of such artifacts and of the hemodynamic relevance of a fetal arrhythmia by alternative methods is necessary for management and therapy. A 28-year-old healthy woman was referred at 30 weeks of gestation because of fetal tachy-brady-arrhythmia, but cw-Doppler assessment of umbilical artery blood flow revealed periods of pseudobradycardia during bigeminal and trigeminal fetal pulse. FHR turned to regular tachycardia, and transplacental digitalization was started. Between 32 and 34 weeks the patient discontinued her digitalis intake, and a fetal pericardial effusion indicated subsequent cardiac failure. Serial pulsed Doppler measurements of fetal aortic blood flow were performed and imminent heart failure was recognized after the digitalis was discontinued and before a pericardial effusion occurred. Furthermore, improvement of fetal cardiac performance secondary to restarting digitalis and also prior to resolution of the pericardial effusion. After spontaneous delivery a Wolff-Parkinson-White syndrome was diagnosed, and continuation of digoxin treatment was indicated. Cw-Doppler assessment of umbilical artery blood flow was a suitable method to evaluate questionable FHR recordings, and pulsed Doppler allowed monitoring of the therapeutic effect of transplacental digitalization by serial measurements of fetal aortic blood flow.

Adult↗

Determining carpal collapse. An improved method.

The carpal height index (carpal height ratio of the diseased wrist divided by that of the normal wrist, as described by Kato et al.) was calculated in forty normal subjects, ten patients who had Stage-III lunatomalacia, and eight patients who had non-union of a fracture of the scaphoid. The method of Youm et al. for determining the carpal height index was altered to include the use of defined points of reference and a standardized radiographic technique. Two tests of reproducibility demonstrated the reliability of the method. The carpal height index was found to be superior to the carpal height ratio for the evaluation of unilateral disease. The mean carpal height index of diseased wrists differed significantly from that of normal wrists. The carpal height index (for unilateral disease) or the carpal height ratio (for bilateral disease) can be used to describe the progression of collapse of the wrist quantitatively and to evaluate and compare various forms of treatment.

Adolescent↗

[Identification of health endangering substances in air pollution].

In a health-related evaluation of the environment, timely recognition of possible health hazards is of much greater significance than describing health injuries that have already occurred. The following model has been found to be workable: The entire study consists of 4 parts which are quite significant when compared with each other and analyzed statistically. (1) Detailed interviews with physicians in practice in the area examined (2) Spirometric tests among school children in third and fourth grades (elementary school) (3) Questionnaires to be completed by the parents of the school children examined, in which the questions implied in (1) are also included. (4) The results obtained are compared to the available data pertaining to the air quality in the region. Possible exposure to adverse indoor conditions in schools and homes are also taken into consideration.

Adolescent↗

[Present status and place of sialography].

Roentgenography without contrast media and sialography, as well as the basic facts concerning the radiodiagnostic of the salivary gland, are all discussed with regard to the most current equipment, examination techniques, the positioning of patients, and the problems involved in contrast media. The technique used in more than 4,000 sialograms is recommended. The diagnostic value of this method is illustrated by means of representative patient series: sialolithiasis, inflammatory disorders, and tumors. The limitations of the method are demonstrated and complementary examinations shown.

Dilatation, Pathologic↗