Factors relating to the sensory acuity of limbs with peripheral vascular insufficiency

We examined several possible causes for the high incidence of poor sensory acuity in the limbs of 176 patients with moderate to severe peripheral vascular insufficiency. We investigated the relationships of diabetes, alcoholism, and smoking, as well as the severity of peripheral vascular disease, to the integrity of basic sensory modalities such as two-point discrimination and perception of light touch. The presence or absence of diabetes exerted the strongest effect on peripheral sensation. In patients who did not have diabetes, sensation in the limbs was most strongly affected by whether the patient was an alcoholic. Smoking did not have a significant effect on limb sensation. Among nondiabetic, nonalcoholic patients, there was a weak residual effect related to the severity of the peripheral vascular insufficiency. Even among these patients, however, systemic factors predominated in determining the loss of sensation. We also examined the extent to which loss of sensation might be related to the development of ulcers. Among patients who were not diabetic, there was a highly significant relationship between loss of sensation and the presence of limb ulceration. Surprisingly, however, there was no discernable relationship between the presence of ulcers in diabetic patients and the degree of loss of peripheral sensation. This result suggests that a large percentage of ulcers seen in diabetic patients are not of neurogenic origin.     

Zur Kenntniss der heterologen Flimmercysten

Ohne Zusammenfassung     

Retroperitoneal rhabdomyosarcoma revealed by acute kidney failure in children. Report of a case

Retroperitoneal sarcomas are rare tumors representing 0.1% to 0.2% of all malignant tumors. They are usually revealed by an abdominal mass (33%), possibly associated with pain (41%). Edema of the lower limbs is reported in 10% of cases. Acute renal failure with anuria by bilateral ureteral compression, associated with invasion of the inferior vena cava has not been previously reported.     

Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.     

Cardiac inotropic responses to calcium and forskolin are not altered by prolonged isoproterenol infusion.

Effects of prolonged isoproterenol infusion upon the density of cardiac calcium channels, calcium-mediated contractile responses, and the ability of forskolin to enhance tension development and cyclic AMP accumulation were studied in ventricular muscle preparations from Sprague-Dawley rats. Isoproterenol infusion (400 micrograms/kg per h s.c., 4 days) significantly decreased calcium channel density (Bmax) in cardiac microsomal membranes as quantified by a 32% decrease in specific [3H]nitrendipine binding sites; binding affinity (KD) was unchanged. A 57% decrease of beta-adrenoceptors confirmed homologous down regulation. To examine functional effects of decreased [3H]nitrendipine binding sites, responses to calcium, BAY K8644 and nifedipine were determined in isolated right ventricular strips. Significant decreases in basal developed tension were observed in muscles from isoproterenol-infused rats. However, concentration-dependent increases in contractility in response to CaCl2 or BAY K8644 were comparable, and the negative inotropic effect of nifedipine was unchanged. Whereas isoproterenol infusion was associated with significantly decreased basal cardiac cyclic AMP concentrations, exposure of ventricular strips from either vehicle- or isoproterenol-infused rats to 10 microM forskolin resulted in comparable increases in cyclic AMP and in developed tension. Cumulative, submaximal concentrations of forskolin also produced similar increases in contractility with maximum responses in ventricular strips from vehicle-infused animals attained at 4.4 microM forskolin. Higher concentrations resulted in automaticity. By contrast, ventricle from isoproterenol-infused animals responded to 14.4 microM forskolin with maximal increases in force of contraction.     

Cell-mediated immune responses in vitro. V. A comparative study of in vitro immunogenicity of splenic lymphocytes, neoplastic lymphoid cells and fibroblats

This study compares the effectiveness of mouse lymphocytes, neoplastic lymphoid cells or fibroblasts in stimulating allogeneic cells to embark on an in vitro cytotoxic response, as measured by a ⁵¹Cr release assay. In addition, during ontogeny of mouse spleen cells, their capacity to stimulate in the mixed lymphocyte culture (MLR) was compared to their capacity to stimulate cytotoxic allograft responses. During ontogeny, there was amarked increase in the capacity of mouse spleen cells to stimulate mitotic responses in the MLR. In contrast, the magnitude of cytotoxic allograft responses induced by neonatal mouse spleen cells in the cytotoxic allograft system was comparable in magnitude to that induced by spleen cells of adult mice. The immunogenicity of subpopulations of mouse spleen cells was investigated. Mouse lymphoid cell populations, enriched for B or T lymphocytes or hemopoietic stem cells were equally immunogenic in vitro, as were myeloma or thymoma lymphoid cells. In contrast, mouse fibroblasts were found to elicit poor cytotoxic allograft responses. In fact, lymphoid cells were about 20–40-fold more immunogenic than fibroblasts.     

Präzisierung der Reizwirkung mittelfrequenter Wechselströme

Zusammenfassung Bei der Mittelfrequenz-Impuls-Reizung ist streng darauf zu achten, daß keine polaritären Reizkomponenten auftreten. Die diesbezügliche Kontrolle wird am besten mit Hilfe des Konvertibilitätstestes vorgenommen, d. h., es darf beim Vertauschen der Zuführungen zu den Reizelektroden weder die Reizschwelle bzw. die Größe des kollektiven Reizerfolges noch dessen Latenzzeit eine signifikante Änderung erfahren. Auf diese Weise wird die Phasenunabhängigkeit des echten Mittelfrequenz-Reizeffektes nachgewiesen.Diesen Anforderungen entsprechen Mittelfrequenz-Impulse, deren Trägerfrequenz über einige wenige Perioden sich aufschaukelt und ebenso wieder abklingt. Demgegenüber sind Mittelfrequenz-Stromstöße mit phasenstarrem Einsatz und Ende nicht unbedingt frei von polaritären Ein- bzw. Ausschalt-effekten, indem sowohl die erste als auch die letzte Trägerperiode einen polaritären Wechselimpuls-Reizeffekt ergeben kann, je nach Phasenlage bezogen auf die wirksame Reizelektrode und Art der Ansprechbarkeit des Reizobjektes (Nerv) auf entsprechend kurze gleitspiegelsymmetrische Wechselimpulse. Für eine echte Mittelfrequenz-Stromstoß-Reizung ist demnach ebenfalls ein Aufschaukeln und Abklingen der Trägerfrequenz über einige wenige Perioden erforderlich.Es besteht ein prinzipieller Unterschied zwischen der echten Mittelfrequenz-Reizung, die phasen -bzw. periodenunabhängig ist und schon früher als apolaritär bezeichnet wurde, und der konventionellen polaritären Reizung, die als polaritäre Komplikation der Mittelfrequenz-Reizung auftreten kann.Diese Präzisierung der Reizwirkung mittelfrequenter Wechselströme wurde angeregt durch zwei im Text erwähnte Publikationen, in denen in keineswegs überzeugender Weise versucht wird, die Mittelfrequenz-Reizung letzten Endes auf das polare Gesetz der Erregung zurückzuführen.

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Summary The particular excitatory action exerted by middle-frequency alternating current can only be revealed if care is taken to eliminate the occurrence of so-called polarity effects. Such effects are produced by the short alternating impulses represented by the first and the last period of a middle-frequency current pulse and are based on the polar law of excitation.In order to prevent such polarity intrusions, it is necessary to increase and decrease the amplitude of the middle-frequency current pulses over a few carrierperiods, or, to use amplitude-modulated middle-frequency impulses of variable shape and duration of envelope.A true middle-frequency excitatory effect is easily demonstrated by resorting to the convertibility test. It will then become evident that stimulation threshold, magnitude as well as latency of response do not change during reversal of the stimulating poles. This means, that no significant phase change of the response with regard to the carrier-frequency occurs when the leads to the stimulating electrodes are commuted, and that, as a result, true middle-frequency effects do not depend upon one particular catelectrotonic variation among the carrier-periods of a middle-frequency current pulse.It can thus be concluded that a fundamental difference exists between true middle-frequency stimulation, which is based on a non-polarity or apolarity principle, and the conventional stimulation of the polar or polarity type.This paper has been written in the hope of dispelling some errors of interpretation (discussed in the text) tending to ascribe the excitatory effects of middle-frequency impulse stimulation to the classical polar law of excitation.

     

The shift from inpatient care to outpatient care in Switzerland since 2017: Policy processes and the role of evidence

The shift from inpatient care to the ambulatory sector is a central aspiration of European health systems. Despite demonstrated benefits, health reforms have struggled to realize their potential. In this context, we discuss recent hospital sector reforms in Switzerland and analyze the content, process, and role of evidence in the recent introduction of policies to substitute inpatient care with ambulatory care. The prevailing payment system incentivized hospitals to provide unnecessary and costly inpatient services, but federal reform on tariff structures was deemed politically unfeasible. Instead, driven by the pressure to contain costs, cantonal and federal health authorities began to deny reimbursement for selected inpatient procedures in 2017. These regulatory measures were effective in reducing inpatient admissions and health care costs. This case study illustrates that clear, simple messages about hospital sector reform can raise awareness of the need for change. However, the evidence used in the policy process was limited and not critically reviewed. Stakeholders used long-standing international comparisons of inpatient substitution potential to legitimize policies, but not to develop them. The analysis restates the importance of inter- and intranational comparative analyses and institutions such as health observatories and suggests aligning health system governance more proactively with international developments.     

Creatine and creatinine metabolism

The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology. Very recently, a series of new discoveries have been made that are bound to have distinguished implications for bioenergetics, physiology, human pathology, and clinical diagnosis and that suggest that deregulation of the creatine kinase (CK) system is associated with a variety of diseases. Disturbances of the CK system have been observed in muscle, brain, cardiac, and renal diseases as well as in cancer. On the other hand, Cr and Cr analogs such as cyclocreatine were found to have antitumor, antiviral, and antidiabetic effects and to protect tissues from hypoxic, ischemic, neurodegenerative, or muscle damage. Oral Cr ingestion is used in sports as an ergogenic aid, and some data suggest that Cr and creatinine may be precursors of food mutagens and uremic toxins. These findings are discussed in depth, the interrelationships are outlined, and all is put into a broader context to provide a more detailed understanding of the biological functions of Cr and of the CK system.     

Malaria prophylaxis and self-therapy in airline crews

The risk of malaria infection in airline crews is estimated to be 0.5 per 1,000 persons per night in areas with high levels of malaria transmission. Routine chemoprophylaxis for years is not recommended because of possible side effects. Airline crews should therefore use appropriate measures to prevent mosquito bites. In addition, they may need to carry "standby" medication with them to be used for presumptive treatment of a febrile illness if medical attention is not readily available.