Biomedical subjects
Publications and source records attributed to M Studer.
Retransfusion of mediastinal shed blood after cardiopulmonary bypass has markedly reduced requirements of homologous blood or blood products. It also decreased the incidence of early reoperation for bleeding. The additional use of a cell saver has not further reduced blood requirements but it improved the patient's perioperative water balance.
Neurological signs and computed tomographic morphology were compared in 60 patients. The primary neurological deficit was most commonly located in the sacral (n = 31) or lumbar plexus (n = 23) and was most commonly caused by a neoplasm (n = 40). In 78% of the patients it correlated with the lesions detected by computed tomography (CT). CT reliably demonstrates extraspinal mass lesions, but only moderately well predicts functional signs.
Over a period of 15 years, 89 patients (70 male, 19 female) aged 15-76 (mean 48) underwent surgery for acute (64) or chronic (25) dissecting aneurysm type I or II. Early mortality was 18% (16 patients); 8 patients died late (2.8% per year); 8 patients had to be reoperated because of late complications on the aorta. Although very often it is not possible to remove or replace the entire diseased aorta, the goal of the operative procedure is to reduce the risk of rupture by replacing the entry site with a dacron graft. Late reoperation has to be considered if dissection progresses or a new aneurysm develops.
This article studies the self-assessed pre/postoperative course of the psychological condition of 3 patient groups (hernia, aorto-coronary bypass and cancer patients) and healthy controls. Some consequences for clinical work are discussed.
Between 1980 and 1983, 103 patients over the age of seventy (average 72.5 years) underwent cardiac surgery. It comprised 41 aortic valve replacements, 11 mitral valve operations, 7 aortic and mitral valve procedures, 18 valve replacements with concomitant coronary artery bypass grafting, 17 coronary revascularizations, 7 operations for VSD after acute myocardial infarction and 2 procedures for dissecting aneurysm of the ascending aorta. Early mortality was 7.8% and late mortality 10% after a mean follow-up of 29.3 months. Preoperative NYHA-class IV is an incremental risk factor for early and later cardiac death. Early and late results are very satisfactory in patients with isolated valvular lesion, with or without concomitant coronary artery disease, and for isolated coronary atherosclerotic heart disease, whereas there is a high risk of early and late death in patients with multiple valvular lesions or VSD after acute myocardial infarction.
From 1979 to April 1984, 51 patients were reoperated on for postoperative angina pectoris. Three patients died early and 4 late. The cause of death was cardiac in all cases. After the second operation the mean observation period was 24.2 months and the mean functional class 2.0. These results were somewhat worse than was to be expected after the first operation. The single significant risk factor was an ejection fraction reduced below 50%. The indication for reoperation should therefore be confined to patients with severe angina, good left-ventricular function, bypassable coronary arteries and sufficient graft material available (saphenous vein, internal mammary artery).
Previous work from our laboratories has indicated that the DNA content of rat cerebral cortex neurons increases postnatally to a level of slightly above 3c, where 2c denotes the diploid DNA complement. We have re-evaluated this concept by using various cytophotometric assays and a novel high performance liquid chromatography (HPLC) technique. The latter consists of digesting the DNA in isolated neuronal nuclei by a mixture of DNA-degrading enzymes followed by analysis of the resulting deoxynucleosides by HPLC. We find that the various methods fall into two groups. The first gives evidence of a postnatal DNA (or histone) increase, while the second does not. The first group (DNA increase) comprises cytofluorometry for DNA following Schiff-type staining with fluorochromes 2,5-bis-(4-aminophenyl)-1,3,4-oxadiazole (BAO) and pararosaniline, ultraviolet absorption scanning for DNA and cytofluorometry for histones following staining with sulfaflavine at pH 8. The second group (no DNA increase) consists of cytofluorometry for DNA following staining with the DNA-complexing agents mithramycin, chromomycin A3, 4',6-diamidino-2-phenylindole (DAPI) and bisbenzimide (Hoechst 33258), as well as the newly developed HPLC technique. Since the HPLC technique measures DNA by a direct chemical approach without interference from other nuclear constituents or from higher order packaging in the chromatin, and detects at least 94-95% of the total DNA contained in neuronal nuclei independent of the developmental stage, we infer that the HPLC technique and, by consequence, the cytochemical assays of the second group reflect true DNA values. Therefore, we propose that cerebral cortex neurons retain a diploid DNA level throughout development.
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The anatomic and functional characteristics of 310 consecutive patients undergoing repair of atrioventricular (AV) septal defects were studied. The characteristics of the six leaflets of the common (139 patients) or two-orifice (171 patients) AV valve are described. Interventricular communications were present in 156 patients and major associated cardiac anomalies in 73 (tetralogy of Fallot 20, double-outlet right ventricle nine, and others). Fifty-one patients (16%) died in hospital. The incremental risk of young age disappeared after 1976. Severity of preoperative AV valve incompetence and New York Heart Association (NYHA) functional class affected hospital mortality. Current risks for patients without major associated cardiac anomalies are 0.6% to 4% for patients in NYHA Class III without an interventricular communication, depending on the degree of preoperative AV valve incompetence, and 5% to 13% for such patients with an interventricular communication. Actuarial survival at 12 1/2 years postoperatively is 95% when preoperative AV valve incompetence is absent or mild and 88% when it is more severe (Grade 3, 4, or 5). Actually, 92% of hospital survivors are alive and in NYHA class I or II. Failure of the AV valve repair occurred in 32 (10%) of the 310 patients and occurred more frequently when AV valve incompetence was severe preoperatively. Its frequency is reduced by current repair techniques, except in patients without interventricular communication.
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The synthesis of a protected bifunctional analog of ethylenediaminetetraacetic acid (EDTA) is described. The molecule contains an aminobenzyl moiety that allows the easy attachment of the chelating agent to a wide variety of groups. Examples of reaction with the C-termini of two peptides are given. In the following paper, the two peptides are used to study the enzymatic cleavage of metal chelates from a monoclonal antibody.
Insight into the metabolism of radiolabeled antibodies is important for the design of better radioimaging and therapy agents. To test the effect of linkers that can be cleaved in vivo, we introduced Ala-Leu-Ala-Leu between the antibody Lym-1 and an 111In-labeled benzyl-EDTA. For comparison, we studied a conjugate without the linker. Digestion of the two conjugates in vitro showed that the one with Ala-Leu-Ala-Leu was cleaved rapidly by the liver protease cathepsin B1 (T1/2 approximately 6 h). After 100 h of digestion, reversed-phase HPLC product analysis of the Ala-Leu-Ala-Leu conjugate showed that 48% of the total radioactivity had the same retention time as (p-aminobenzyl)-EDTA(In), and 37% of the total radioactivity had the same retention time as [p-(Ala-Leu-amido)benzyl]-EDTA(In). After 97 h of digestion, the conjugate without the linker had 79% of the radioactivity activity still attached to the protein. We also tested the two conjugates in mice. Ala-Leu-Ala-Leu had only a moderate effect on the whole body and liver clearance in vivo. The excretion of the radioactivity was about 6% per day with the linker and about 3% per day without the linker. HPLC analysis of the urine of a single mouse showed products similar to the in vitro study; 54% of the excreted radioactivity had the same retention time as (p-aminobenzyl)-EDTA(In), while 10% had the retention time of [p-(Ala-Leu-amido)benzyl]-EDTA(In).
Segmentation of the vertebrate hindbrain into rhombomeres is important for the anterior-posterior arrangement of cranial motor nuclei and efferent nerves. Underlying this reiterated organization, Hox genes display segmentally restricted domains of expression, such as expression of Hoxb-1 (refs 5, 6) in rhombomere 4 (r4). Here we report that absence of Hoxb-1 leads to changes in r4 identity. In mutant mouse embryos, molecular markers indicate that patterning of r4 is initiated properly but not maintained. Cellular analysis by DiI tracing reveals that the r4-specific facial branchiomotor (FBM) and contralateral vestibuloacoustic efferent (CVA) neurons are incorrectly specified. In wild-type mice CVA neurons migrate from r4 into the contralateral side, and we found in lineage analysis that FBM neurons migrate from r4 into r5. In mutants, motor neurons differentiate but the CVA and FBM neurons fail to migrate into their proper positions. Instead, they form a motor nucleus which migrates atypically, and there is a subsequent loss of the facial motor nerve. These results demonstrate that, as a part of its role in maintaining rhombomere identity, Hoxb-1 is involved in controlling migratory properties of motor neurons in the hindbrain.