Biomedical subjects
Publications and source records attributed to S Gasser.
Sepsis is the most important reason for death among intensive care patients. This review will cover the actual definition of septic shock, and the difficulties regarding the diagnosis of sepsis. The principles of management of sepsis, the recently established principles as early goal directed therapy, low dose steroid substitution, insulin therapy, and the activated protein C are discussed.
The classical description of porous media as a homogeneous equivalent fluid is presented, and its foundations on the homogenization method is introduced and applied to the numerical prediction model for a periodic porous medium composed by face centered cubic sphere packing on which measurements have been made. The results are compared with existing numerical results in the literature and with new and experimental data.
Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic. Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila c-myc mutants, which are smaller as a result of hypotrophy. We find that c-myc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size.
We have prepared transgenic mice whose T cells constitutively express a chimeric receptor combining extracellular human IL-4R and intracellular IL-2Rbeta segments. This receptor can transmit IL-2/IL-15-like signals in response to human, but not mouse, IL-4. We used these animals to explore to what extent functional IL-2R/IL-15R expression controls the capacity of T cells to proliferate in response to IL-2/IL-15-like signals. After activation with Con A, naive transgenic CD8+ and CD4+ T cells respond to human IL-4 as well as to IL-2. Without prior activation, they failed to proliferate in response to human IL-4, although human IL-4 did prolong their survival. Thus, IL-2-induced proliferation of activated T cells requires at least one other Ag-induced change apart from the induction of a functional IL-2R. However, a fraction of CD8+CD44high T cells proliferate in human IL-4 without antigenic stimulation or syngeneic feeder cells. In contrast, CD4+CD44high T cells are not constitutively responsive to human IL-4. We conclude that although all transgenic T cells express a functional chimeric receptor, only some CD8+CD44high T cells contain all molecules required for entry into the cell cycle in response to human IL-4 or IL-15.
In a double-blind randomized study, the suppression of ovarian activity, the effects on the cervix and endometrium, menstrual bleeding patterns and overall tolerance were assessed during administration of two low-dose oral contraceptives (20 micrograms ethinylestradiol EE, 500 micrograms norethisterone--Eve 20, Grünenthal, Aachen; 20 micrograms EE, 150 micrograms Desogestrel--Lovelle, Organon, Munich), 118 healthy women (ages: 18 to 35 years) with comparable bioprofiles (height, weight, menstrual cycle patterns) were studied in 10 investigation centres during medication with either Eve 20 (n = 59) or Lovelle (n = 59). During 3 treatment cycles, ovarian activity was evaluated by sonographic determination of follicular size and by simultaneous assessment of serum endocrine profiles (gonadotropins LH and FSH, ovarian steroids estradiol [E2] and progesterone [P]). Treatment cycles 4 to 6 served to evaluate the patterns of menstrual bleeding and the overall subjective tolerance on each contraceptive. While on the preparations, no ovarian activity (as judged by a lack of follicular growth and suppressed sex steroid levels) was found in over 90% of all investigated cycles. Follicular activity and/or cyst formation were detected in 18 of 173 cycles (Eve 20) and in 5 of 175 cycles (Lovelle) respectively. Gonadotropin levels were suppressed (LH < 6 IU/l, FSH < 8 IU/l) in most treatment cycles (Eve 20: 76.6% vs. Lovelle: 84.8%). Serum E2 concentrations exceeding 0.1 nmol/l indicated residual follicular activity in 19.3% (Eve 20) vs. 12.2% (Lovelle) of all cycles. As estimated by serum P levels over 5 nmol/l, ovulation had presumably occurred in 4.1% (Eve 20) vs. 2.9% (Lovelle) of treatments respectively. However, when the sonographic and endocrinological data were combined, no ovulation was documented in any treatment cycle. In addition, the quality of the cervical mucus was minimal and a low endometrial thickness was found in the majority of women, indicating strong progestogen effects of both contraceptives. Menstrual irregularities (intermenstrual spotting, break-through bleeding) occurred initially on each preparation, but were mostly resolved when the pills were continued. The acceptance of each investigated drug was rated as very good or good by most subjects. These observations allow us to conclude that the rate of ovarian suppression with inhibition of follicular activity is high under low-dose oral contraceptives. The different progestogens as components of these contraceptive pills display equally good anti-conceptive effects on both the cervix and the endometrium. Furthermore, the rate of irregular menstrual bleeding is acceptable for these low-dose contraceptives. The high acceptance of each preparation suggests that such agents will have a high rate of acceptability in clinical use.
Yeast chromosomes may lack the linker histone H1 (normally required to compact 10 nm beads-on-a-string fiber into the 30 nm fiber) and there is no cytological evidence for higher order fiber structure but they do contain regions which correspond to euchromatin and heterochromatin of higher eukaryotes. Both euchromatin and heterochromatin contain nucleosomal particles (composed of two molecules each of H2A, H2B, H3 and H4), however histones have been shown to regulate genes in these regions in quite different ways. The mechanisms by which such regulation occurs are the topic of this paper.
Leprosy was once a severely mutilating and incapacitating disease with little hope for the afflicted. Today, patients with leprosy do not suffer from the obvious deformities seen in earlier days, so recognition of this disease has become more difficult. We report the case of a man with no previous disabilities who presented to the emergency department with acute unintentional hand trauma secondary to peripheral neuropathy caused by leprosy.
The purpose of this study was to determine the position and relative safety of the anterior, posterior, and newly defined middle portals by measuring their distance from the neurovascular structures and tendons on the lateral side of the foot and ankle. Furthermore, this study demonstrates specific components of the posterior subtalar joint and arthroscopic access to each utilizing a technique that allows direct anatomic correlation. The 15 specimens were divided into three groups of five feet each, with one arthroscopic portal site and one instrumentation portal site per group. Group I used the anterior portal for the arthroscope and the posterior portal for the curette. Group II used the posterior portal for the arthroscope and the anterior portal for the curette. In group III, the arthroscope was inserted through the anterior portal and the curette through the middle portal. The sural nerve and small saphenous vein were at risk with posterior portal placement. The anterior portal presented a minor risk of injury to the dorsal intermediate cutaneous branch of the superficial peroneal nerve. The middle portal was without risk to surrounding structures. Group I provided the best access to the posterior facet of the subtalar joint. Group II provided excellent arthroscopic visualization of the posterior facet, but poor access for instrumentation via the anterior portal. Group III provided the best access to the sinus tarsi. No combination of portals allowed visualization or instrumentation of the middle or anterior facets.
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Thirty-three patients who had a maligned non-union of the tibial diaphysis were treated by limited open exposure, indirect reduction with a femoral distractor, tension-band plating, lag-screw fixation, and autogenous bone-grafting. The time from the injury to treatment of the non-union averaged twenty-nine months. Twenty-two of the fractures were originally open and sixteen fractures had had a previous infection before treatment of the non-union. The non-unions were classified as hypertrophic in eight patients, oligotrophic in eighteen, and atrophic in seven. All had severe deformity, or the nature or level of the non-union, or both, precluded intramedullary nailing as a treatment option. All thirty-three non-unions healed at an average of four months; the average length of follow-up was nineteen months. The deformity was corrected, within acceptable limits, in thirty-two of the patients. Full motion of the knee was achieved in twenty-nine patients and of the ankle, in eighteen. Complications included four instances of superficial skin breakdowns, one deep infection, and one fracture of the plate. For non-unions of the tibial diaphysis with deformity that are not amenable to intramedullary nailing, the techniques of limited exposure, indirect reduction, tension-band plating, and bone-grafting can yield excellent anatomical and functional results.
We report on a 14 year-old boy with 48,XXYY karyotype, presenting with essential tremor and a slight retardation of psychomotor development. In contrast to other cases with 48,XXYY syndrome, this pubertal patient has testicles of normal size, has small stature and shows no behavioural disturbances. We compared our patient with 120 other published cases.
In the present study, we have optimized an immunocytochemical ultrastructural approach for in situ localization of newly synthesized DNA in unsynchronized as well as in synchronized human HeLa cells and in exponentially growing mouse P815 cells, which had incorporated bromodeoxyuridine (BrdU) during short pulses varying from 1 to 20 minutes. The incorporated BrdU was detected in hydrolyzed ultrathin cryosections or Lowicryl sections by means of a monoclonal antibody, revealed by secondary colloidal gold-labeled probes. The results demonstrate our ability to study, with high resolution and reproducibility, DNA replication during consecutive periods of the S-phase, which is monitored by the incorporation of tritiated thymidine. In addition, this approach allows one to perform a concomitant mapping of replicated DNA and various enzymes of the replisome.
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The yeast mitochondrial outer membrane was isolated and 10 of its major polypeptides were identified (mol. wts. 109, 70, 57, 45, 45, 42, 33, 29, 25 and 14 kd). The membrane has no major polypeptide in common with either mitochondrial inner membrane or rough microsomes. Protease treatment and immunochemical techniques showed that virtually all of the isolated outer membrane vesicles are sealed and display the same surface orientation as in the intact mitochondrion.