Prudent strategies for elective red blood cell transfusion.

OBJECTIVE: To review the literature on the appropriateness of red blood cell transfusion and current physician practice, with emphasis on the physiologic and symptomatic implications of elective transfusion in the treatment of anemia. DATA SOURCES: Studies on the therapeutic use of red blood cell transfusion were identified through a search of MEDLINE (1966 to the present) and through a manual review of bibliographies of identified articles. In addition, evidence was solicited from selected experts in the field and recent consensus panels that have developed transfusion guidelines. DATA SYNTHESIS: No controlled trials of blood transfusion were identified, but data were available on four issues relevant to transfusion practice: current physician practice and evidence for excessive use of red blood cell transfusion; physiologic adaptation to anemia; human tolerance of low hemoglobin levels; and strategies for reducing homologous transfusion requirements. CONCLUSIONS: Despite the recent decline in red blood cell use because of concerns about infection, current transfusion practice remains variable because physicians have disparate views about its appropriateness. The remarkable human tolerance of anemia suggests that clinicians can accept hemoglobin levels above 70 g/L (7 g/dL) in most patients with self-limited anemia. In patients with impaired cardiovascular status or with anemias that will not resolve spontaneously, however, the data are insufficient to determine minimum acceptable hemoglobin levels, and therapy must be guided by the clinical situation. Several therapeutic strategies and pharmacologic interventions are available in the perioperative and non-operative settings to further reduce red blood cell use.     

Use of the silver nucleolar organizer region (AgNOR) technique in the differential diagnosis of central nervous system neoplasia.

Because the distinction between gliosis and low-grade astrocytoma may prove difficult by routine light microscopy, we evaluated the silver nucleolar organizer region (AgNOR) technique in making this distinction. The AgNOR impregnation was performed on formalin-fixed, paraffin-embedded tissue from 49 central nervous system (CNS) biopsies: eight normal brain, 14 gliosis, 14 grade 2 astrocytoma (Daumas-Duport scale), two grade 4 astrocytoma, nine medulloblastoma, one metastatic carcinoma, and one choroid plexus papilloma. Quantitative and qualitative differences were found between gliosis and low-grade astrocytomas. In gliosis, AgNOR counts averaged 1.18 +/- 0.11 (SD) AgNOR/nucleus, while in low-grade astrocytomas AgNOR counts averaged 2.22 +/- 0.39 (p less than 0.001). Compound AgNOR were frequent in 9/14 grade 2 astrocytomas and in both grade 4 astrocytomas, whereas compound AgNOR were extremely rare in cases of gliosis. Quantitative and qualitative differences were also found between normal cerebellar internal granular cells and medulloblastoma cells. Cerebellar granular cells averaged 0.90 +/- 0.10 AgNOR/nucleus whereas medulloblastoma cells had an average of 4.52 +/- 0.95 (p less than 0.001). Compound AgNOR were seen in all medulloblastomas but not in internal granular cells. These findings suggest that the AgNOR technique may be a useful adjunct in the diagnosis of CNS neoplasia.     

A personal computer database system for head and neck cancer records

The computerized database system described was initially developed in 1986 to facilitate analysis of retrospective head and neck cancer data from the Royal Adelaide Hospital Department of Otolaryngology. This has now been expanded to become an on-going patient information management system. It is based on the dBase-III-Plus database package and is implemented on an IBM XT compatible computer. The system was designed to be used by staff without specialist computer skills and is therefore largely “menu-driven.” The main functions include patient record creation, update, and retrieval, and the production of reports including graphical presentations. There is also a powerful but easy to use query facility. The system has already provided much useful epidemiological material but is now beginning to fulfill an even more important role in patient follow-up and in assisting evaluation of alternative treatment protocols.     

Involvement of Ca+ mobilization in the amplifying effect of serotonin on responses of rabbit isolated ear artery to exogenous noradrenaline

Summary The present study examined the involvement of Ca⁺ mobilization in the amplifying effect of serotonin on steady-state responses of rabbit isolated perfused ear artery to exogenous noradrenaline (NA; 0.001–3 ol/l). In contrast to its marked amplifying effect on responses to NA, serotonin in the subconstrictor concentration of 100 nmol/l had no effect on responses to KCl. The Ca⁺-entry blocking drug diltiazem (10 gmol/1) decreased responses to NA; in addition, the amplifying effect of serotonin on responses to NA was reduced by diltiazem. Lowering the concentration of Ca⁺ in the Krebs-Henseleit perfusion solution from 2.5 to 0.25 mmol/l also reduced both responses to NA and the amplifying effect of serotonin. Using the method of Manzini et al. (1982), separate intra- and extracellular Ca⁺-dependent responses to NA were obtained. Serotonin had no effect on intracellular Ca⁺-dependent responses to NA but enhanced extracellular Ca²⁺-dependent NA responses. These results suggest that the amplifying effect of serotonin on responses of rabbit ear artery to exogenous NA involves a selective enhancement of the component of the NA response which is dependent on extracellular Ca⁺; serotonin may increase NA-evoked entry of Ca²⁺ into the vascular smooth muscle cells through receptor-operated Ca⁺ channels. Send offprint requests to A. G. Meehan at the above address     

Operation Everest II: Alterations in the immune system at high altitudes

We investigated the effects on immune function after progressive hypobaric hypoxia simulating an ascent to 25,000 ft (7620 m) over 4 weeks. Multiple simultaneousin vitro andin vivo immunologic variables were obtained from subjects at sea level, 7500 ft (2286 m), and 25,000 ft during a decompression chamber exposure. Phytohemag-glutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells were reduced at extreme altitudes. Mononuclear-cell subset analysis by flow cytometry disclosed an increase in monocytes without changes in B cells or T-cell subsets. Plasma IgM and IgA but not IgG levels were increased at altitudes, whereas pokeweed mitogen-stimulatedin vitro IgG, IgA, and IgM secretion was unchanged. During exposure to 25,000 ft,in vitro phytohemagglutinin-stimulated interferon production and natural killer-cell cytotoxicity did not change statistically, but larger intersubject differences occurred. IgA and lysozyme levels (nasal wash) and serum antibodies to nuclear antigens were not influenced by altitude exposure. These results suggest that T-cell activation is blunted during exposure to severe hypoxemia, whereas B-cell function and mucosal immunity are not. Although the mechanism of alteredin vitro immune responsiveness after exposure to various environmental stressors has not been elucidated in humans, hypoxia may induce alterations in immune regulation as suggested byin vitro immune assays of effector-cell function.Some of this study's results were presented as an abstract at the FASEB meeting in St. Louis, Missouri, 1986.     

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.