Preoperative autologous blood donation: benefit or detriment? A mathematical analysis

BACKGROUND: Advocates of preoperative autologous blood donation (PABD) often fail to consider the needs of individual patients and the effects of donation on hematocrit. Mathematical modeling is used here to analyze PABD. STUDY DESIGN AND METHODS: A model of PABD was constructed to simulate the transfusion of red cells once a predetermined minimum hematocrit was reached. Preoperatively deposited units not needed to maintain a hematocrit at this level were not transfused. Final hematocrits were compared to the hematocrit that would be expected if the patient had not donated blood for his or her own operative use. RESULTS: For many patients, particularly those with normal initial hematocrits, large estimated blood losses must occur before the minimum hematocrit is reached. It is also known that patients donating multiple units typically cannot maintain their baseline hematocrit. In such cases, for blood losses of any volume, the final hematocrit was lower if units were collected preoperatively and transfusion did not occur. Preoperatively donating patients are more likely to be transfused earlier and more frequently than nondonating patients. Derived figures, based on individual patient values, help predict which patients will benefit most from PABD. CONCLUSION: PABD may actually lead to decreased postoperative hematocritis (with enhanced risk of ischemia) and otherwise unnecessary transfusions.     

Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67

To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki- 67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.     

24-hour oesophageal two-level pH monitoring in healthy children and adolescents

Two-level pH recording in the oesophagus was performed for 24 h in 28 healthy schoolchildren between 9.3 and 17.3 years of age, to obtain reference values for reflux studies. The pH probes were placed 5 and 15 cm above the lower oesophageal sphincter by means of the manometric technique. A standardized acid-free diet was given on the day of recording. A drop in pH to 4.0 or below was regarded as reflux. The normal upper limit of total reflux time was 1.0% at the lower oesophageal level. Mean reflux time was about three times shorter at the upper level than at the lower, which indicates the importance of exact positioning of the pH probe.     

Localization of glucocorticoid receptor mRNA in the male rat brain by in situ hybridization.

The localization and distribution of mRNA encoding the glucocorticoid receptor (GR) was investigated in tissue sections of the adult male rat brain by in situ hybridization and RNA blot analysis. GR mRNA levels were measured by quantitative autoradiography with 35S- and 32P-labeled RNA probes, respectively. Strong labeling was observed within the pyramidal nerve cells of the CA1 and CA2 areas of the hippocampal formation, in the granular cells of the dentate gyrus, in the parvocellular nerve cells of the paraventricular hypothalamic nucleus, and in the cells of the arcuate nucleus, especially the parvocellular part. Moderate labeling of a large number of nerve cells was observed within layers II, III, and VI of the neocortex and in many thalamic nuclei, especially the anterior and ventral nuclear groups as well as several midline nuclei. Within the cerebellar cortex, strong labeling was observed all over the granular layer. In the lower brainstem, strong labeling was found within the entire locus coeruleus and within the mesencephalic raphe nuclei rich in noradrenaline and 5-hydroxytryptamine cell bodies, respectively. A close correlation was found between the distribution of GR mRNA and the distribution of previously described GR immunoreactivity. These studies open the possibility of obtaining additional information on in vivo regulation of GR synthesis and how the brain may alter its sensitivity to circulating glucocorticoids.     

Sex ratio adjustment in relation to paternal attractiveness in a wild bird population.

When the relative fitness of sons and daughters differs, sex-allocation theory predicts that it would be adaptive for individuals to adjust their investment in different sexes of offspring. Sex ratio adjustment by females in response to the sexual attractiveness of their mate would be an example of this. In vertebrates the existence of this form of sex ratio adjustment is controversial and may be confounded with sex-biased mortality, particularly in sexually size-dimorphic species. Here we use PCR amplification of a conserved W-chromosome-linked gene to show that the sex ratio within broods of a natural population of sexually size-monomorphic collared flycatchers Ficedula albicollis is related to the size of their father's forehead patch, a heritable secondary sexual character implicated in female choice. Experimental manipulations of paternal investment, which influence the size of his character in future breeding attempts, result in corresponding changes in the sex ratio of offspring born to males in those breeding attempts. In contrast, manipulations of maternal investment have no effect on future sex ratios, and there is no relationship between variables predicting the reproductive value of the brood and nestling sex ratio. Analysis of recruitment of offspring reveals similar patterns of sex ratio bias. The results suggest that female collared flycatchers be able to adjust the sex ratio of eggs ovulated in response to the phenotype of their mate. This finding is most consistent with "genetic quality" models of sexual selection.     

Frequent somatic deletion of the 13q12.3 locus encompassing BRCA2 in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) has consistent 13q chromosomal abnormalities detected by conventional cytogenetics. Using interphase cytogenetics we show deletion of a 1-megabase 13q12.3 locus, encompassing the BRCA2 gene, in 80% of 35 CLL cases studied. Homozygous deletion of BRCA2, located within the minimal deletion consensus, was detected in a significant population of cells in 60% of the cases. Deletion of the previously described 13q14 locus (analyzed with RB1 and D13S25 probes) was seen in 63% of the cases. Homozygous deletion of RB1 was seen in one case. Seven of the cases (32%) with D13S25 deletion had a population of cells with homozygous deletion. Deletions at the 13q12 and 13q14 loci result from distinct events because they were not contiguous. These data provide evidence for the existence of a new tumor suppressor locus in B-cell CLL located at 13q12.3. BRCA2, located within the minimal deletion consensus, is a candidate for the gene whose somatic inactivation could play a role in the initiation and or progression of B-cell CLL.     

Granulocyte colony-stimulating factor mobilizes into peripheral blood the complete clonal repertoire of hematopoietic precursors residing in the bone marrow of mice

We have established the clonal relationships between the hematopoietic precursors residing in the bone marrow (BM) and the peripheral blood (PB) of mice treated with granulocyte colony-stimulating factor (G- CSF). The use of animals whose hematopoiesis was reconstituted with genetically labeled stem cells has allowed us to show that an almost identical repertoire of clones is found in the colony-forming unit (CFU- S) population present in the BM and mobilized PB. Moreover, our data has shown that the frequency of expression of the repopulating clones in both types of CFU-S populations is the same, evidencing that G-CSF mobilized PB progenitor cells (PBPCs) closely reflect the clonal make- up of the hematopoietic precursors residing in the BM. When secondary recipients were transplanted with BM or mobilized PB grafts that had been harvested from the genetically marked mice, the presence of long- term lympho-hematopoietic repopulating clones was showed not only in the BM but also in the PB samples. No new clones were identified in the long-term repopulating cells of the mobilized animals with respect to those found in the CFU-S population. Moreover, the hematopoietic precursors that were capable of long-term reconstitution corresponded to the clones, which were most highly represented in the CFU-S compartment, suggesting, at least in the case of G-CSF treated mice, that the frequency of expression of the repopulating clones in the CFU- S population is prognostic for the clone longevity. Based on our experimental data, new advantages for the use of mobilized PBPCs in place of hematopoietic grafts procured from limited areas of BM are proposed.     

On the mechanism of action of the antidepressant drugs amitriptyline and nortriptyline. Evidence for 5-hydroxytryptamine receptor blocking activity

Effects of amitryptyline (AMI) and nortriptyline (NOR) were studied on the [5-³H] hydroxytryptamine ([5-³H]HT) and D-[³H]lysergic acid diethylamide-(D-[³H] LSD) binding in cerebral cortex of rats and on behaviours depedent upon 5-hydroxtrryptamine (5-HT) receptor activity. AMI and NOR were found to have affinity for some of the D-LSD binding sites in the cerebral cortex but no or very weak affinity for the 5-HT binding site. AMI and NOR blocked the 5-hydroxytryptophan (5-HTP) and D-LSD induced head twitches in mice and the D-LSD induced extensor reflex activity. This 5-HT receptor blocking activity of AMI and NOR may in part mediate their antidepressant actions.     

Limited impact of fibromodulin deficiency on the development of experimental skin fibrosis

Excessive production of collagen is the hallmark of fatal diseases of fibrosis such as systemic sclerosis. Overexpression of the proteoglycan fibromodulin (FMOD) has been associated with improved wound healing and scarless repair. In this study, we have investigated the consequences of FMOD deficiency on the development of experimental skin fibrosis. Using immunohistochemistry, we identified FMOD in both human and murine fibrotic skin. In the bleomycin model of skin fibrosis, FMOD^?/? mice developed skin fibrosis to a similar degree compared to FMOD^+/+ mice. Analysis of skin ultrastructure using transmission electron microscopy revealed a significant reduction in collagen fibril diameter in FMOD^?/? but not FMOD^+/+ mice following fibrosis. We conclude that the impact of FMOD deficiency on the development of experimental skin fibrosis is limited.     

The effects on hepatic steroid metabolism of an ectopic pituitary graft: A time study

The time course of feminization of hepatic steroid metabolism in the rat was followed after transplantation of a normal male or female pituitary gland under the kidney capsule of the host animal. Feminization of enzymes active on 4-androstene-3,17-dione and 5α-androstane-3α, 17β-diol occurred between 4 and 8 days after transplantation. Prior to this, masculinization of liver enzyme activities was seen in the transplanted animals. The data on concentrations of lutropin (LH), follitropin (FSH) and prolactin in host serum indicated that, of these hormones, only prolactin was produced by the ectopic pituitary gland. A lag period of 2–4 days was observed before prolactin appeared in host serum. The serum concentrations of prolactin, lutropin and follitropin were poorly correlated with the degree of feminization of hepatic steroid metabolism in the host animal. It thus appears that the ectopic pituitary gland within 4–8 days after implantation begins to secrete (a) factor(s) which is (are) not identical to prolactin, lutropin or follitropin, and which feminize(s) the steroid metabolism in the liver.