[Restricted mobility in nursing home residents : The role of pain and cognitive capacity]. / Mobilitätseinschränkungen bei Altenheimbewohnern : Die Rolle von Schmerz und kognitiver Leistungsfähigkeit.

BACKGROUND: Pain, restriction of mobility and cognitive impairment are often present in old age and intensify each other. OBJECTIVES: Is there a relationship between mobility, pain, cognitive capacity, diagnoses and number of prescribed medication for residents of nursing homes? METHODS: Subgroup analysis of the baseline data from an intervention study for optimization of the medication safety of 120 nursing home residents. RESULTS: Pain was presumed in 77.8% of the residents. Persons with cognitive impairment were more frequently affected. The results of the observational and self-reported pain assessment in cognitively impaired patients did not agree for two-thirds of the cases. A correlation between prevalence of pain, pain intensity and mobility could only be shown for persons without cognitive impairment. Half of the persons were unable to walk; 80% of the residents with analgesics as a permanent medication were more restricted in their mobility. CONCLUSIONS: Cognitive impairment is associated with pain and reduced mobility, whereby self-rated pain did not concur with the observational pain assessment for two-thirds of the residents with cognitive impairment. This illustrates the difficulty of observational pain assessment.

Effectiveness of non-cardiac preoperative testing in non-cardiac elective surgery: a systematic review.

Elective surgery is usually preceded by preoperative diagnostics to minimize risk. The results are assumed to elicit preventive measures or even cancellation of surgery. Moreover, physicians perform preoperative tests as a baseline to detect subsequent changes. This systematic review aims to explore whether preoperative testing leads to changes in management or reduces perioperative mortality or morbidity in unselected patients undergoing elective, non-cardiac surgery. We systematically searched all relevant databases from January 2001 to February 2011 for studies investigating the relationship between preoperative diagnostics and perioperative outcome. Our methodology was based on the manual of the Ludwig Boltzmann Institute for Health Technology Assessment, the Scottish Intercollegiate Guidelines Network (SIGN) handbook, and the PRISMA statement for reporting systematic reviews. One hundred and one of the 25 281 publications retrieved met our inclusion criteria. Three test grid studies used a randomized controlled design and 98 studies used an observational design. The test grid studies show that in cataract surgery and ambulatory surgery, there are no significant differences between patients with indicated preoperative testing and no testing regarding perioperative outcome. The observational studies do not provide valid evidence that preoperative testing is beneficial in healthy adults undergoing non-cardiac surgery. There is no evidence derived from high-quality studies that supports routine preoperative testing in healthy adults undergoing non-cardiac surgery. Testing according to pathological findings in a patient's medical history or physical examination seems justified, although the evidence is scarce. High-quality studies, especially large randomized controlled trials, are needed to explore the effectiveness of indicated preoperative testing.

Abnormal pre-operative tests, pathologic findings of medical history, and their predictive value for perioperative complications.

BACKGROUND: Laboratory tests, electrocardiogram (ECG) and chest X-rays still serve as part of the routine assessment before elective surgery in many institutions, even though there is little evidence of their predictive value relating to perioperative complications. This study investigates the correlation of abnormal findings in pre-operative tests and pathologic findings in the medical history with perioperative complications. METHODS: Patients scheduled for elective surgery in a secondary care hospital were included in this prospective cohort study. Abnormal pre-operative tests, significant findings from the medical history and perioperative complications were recorded. Regression analysis was performed in order to identify the strongest predictors for perioperative complications. RESULTS: A total of 1363 (56.1% female) patients were consecutively included in this study. The percentage of abnormalities in pre-operative tests ranged from 1.6% (electrolytes) and 29.7% (echocardiography). Eighty-six (6.3%) patients had at least one perioperative complication. The most frequent complications were hypo- or hypertension in 55 cases (4.0%), followed by 20 patients (1.5%) who suffered from hemodynamically relevant cardiac dysrhythmias such as supraventricular tachycardia, ventricular tachycardia, bradycardia and ventricular extrasystoles. The binary logistic regression analysis to identify predictors of perioperative complications showed significant results for age, invasiveness of the procedure, history of renal disease or anemia and abnormal ECG. CONCLUSION: Our results indicate that age, type of surgery and medical history are appropriate predictors of perioperative complications, whereas abnormalities in laboratory tests seem to have restricted ability in predicting adverse perioperative outcome.

Soluble ICAM-1 in breast cancer: clinical significance and biological implications.

OBJECTIVES: In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecule I (ICAM-1) on both tumour cells and antigen-presenting cells derived from patients with breast cancer, resulting in an abrogation of antigen presentation and tumour cell lysis. Recently, increased levels of a soluble isoform of ICAM-1 (sICAM-1) have been detected in the sera of breast cancer patients. The present investigation was performed in order to investigate the biological relevance of serum concentrations and the effects of sICAM-1 in patients with breast cancer. PATIENTS AND METHODS: sICAM-1 was determined using a sandwich enzyme immunoassay on sera from 88 patients with various stages of breast cancer and correlated with clinical parameters. The effect of sICAM-1 present in the sera of patients with breast cancer upon unspecific and anti-Her-21/neu antibody-mediated cytotoxicity (ADCC), as well as upon antigen presentation, was determined using a 51Cr-release assay and [3H]thymidine-uptake of T cells after co-incubation with tetanus-toxoid-pulsed antigen-presenting cells. RESULTS: In patients with early breast cancer, serum levels of sICAM-1 were significantly lower compared to patients with metastatic disease, but did not correlate with usual clinical parameters. In patients with metastatic breast cancer, a significant correlation of sICAM-1 with tumour markers CEA and CA 15-3 was observed. No influence of sICAM-1 upon unspecific cytotoxicity, ADCC, or the ability to present antigen was observed. DISCUSSION: The origin of sICAM-1 in the sera of patients with breast cancer remains unknown. In contrast to its membrane-bound isoform, sICAM-1 was increased in the sera of patients with various stages of breast cancer, but its presence did not influence unspecific cytotoxicity, ADCC, or antigen-induced T cell proliferation.

Gemcitabine for relapsed or resistant lymphoma.

BACKGROUND: Gemcitabine therapy has not been widely assessed in the treatment of hematological malignancies. We have examined the efficacy and safety of gemcitabine in patients with relapsed or resistant lymphoma. PATIENTS AND METHODS: Gemcitabine (1 g/m2) was given weekly for 7 consecutive weeks, followed by a week off treatment. The drug was then given for 3 consecutive weeks, followed by a week off treatment; this regimen was continued until disease progression or drug intolerance. Fifteen patients have enrolled. Most have been extensively pre-treated for advanced diffuse large-cell or mantle-cell lymphoma. RESULTS: The drug was well tolerated; no patient suffered treatment-related sepsis, hemorrhage or death. Non-hematopoietic toxicity led to discontinuation of gemcitabine therapy in two patients. Dose reductions or delays were required for about two-thirds of treatments. Of 13 evaluable patients, one had a complete response, 3 a partial response, 3 stable disease, and 6 disease progression. After 6 infusions of gemcitabine, a patient with advanced Hodgkin's disease has had a complete remission lasting 21 months. CONCLUSIONS: Gemcitabine has substantial activity and acceptable toxicity in heavily pre-treated patients with advanced lymphoma. Further study is warranted.

Expression of a cosmid containing the LCR, (A)gamma, delta, and beta globin genes in mouse erythroleukemia cells.

A novel method involving the packaging of phage particles was used to introduce cosmids containing components of the human beta-globin locus control region (LCR) and the human (A)gamma, delta, and beta globin genes into mouse erythroleukemia (MEL) cells. After stable transfection, MEL clones were selected and analyzed for expression of human genes. Both (A)gamma and beta globin mRNA were expressed in these clones, indicating that MEL cells do not suppress transcription of the human gamma globin gene. The variability of human (A)gamma vs. beta globin expression from clone to clone prevents a clear delineation of differences in the expression of these two genes with a cosmid in which a region potentially involved in gamma-to-beta switching has been deleted. The results suggest that MEL cells are capable of supporting human gamma expression, despite their predominantly adult phenotype.

Neoadjuvant chemotherapy (MVAC) in locally invasive bladder cancer.

In order to evaluate the efficacy of neoadjuvant chemotherapy in invasive urothelial carcinoma of the bladder a retrospective analysis was performed. 54 patients without distant metastases (T2-T3b, N0-X, M0) received 3 cycles of neoadjuvant chemotherapy according to the MVAC protocol (methotrexate, vinblastine, doxorubicin and cisplatin) after transurethral resection (TUR) followed by cystectomy. 52 patients had previously undergone cystectomy immediately after TUR. Complete histopathological remission was observed in 9 patients (17.3%) after TUR and in 17 patients (31.5%) after TUR+MVAC. Neoadjuvant MVAC resulted, therefore, in a 14% higher rate of complete remissions. The overall response to TUR was significantly improved by MVAC therapy. Downstaging by neoadjuvant chemotherapy was more readily achieved in initially low-stage tumours (T2: 44.4% and 30.8%, T3a: 47.1% and 19%, T3b: 5.3% and 5.5% in patients receiving TUR+MVAC and TUR alone, respectively). Overall survival did not differ significantly between both groups. Patients who were successfully downstaged to pT0 had a significantly better prognosis, and patients resistant to chemotherapy had the poorest prognosis, showing the shortest survival. In conclusion, histopathological response at cystectomy was improved by neoadjuvant MVAC chemotherapy after TUR and can be expected to be prognostically relevant in those patients who can be downstaged to T0, although overall survival failed to be significantly increased in this relatively small patient sample.

A DNA-binding factor in adult hematopoietic cells interacts with a pyrimidine-rich domain upstream from the human delta-globin gene.

To date, DNA-binding factors with a developmental pattern of expression have not been described in human erythroid cells to explain the switch from fetal (gamma-) to adult (delta- and beta-) globin gene expression. Here we describe a factor present in nuclear extracts from adult mouse and human hematopoietic cells that binds to an oligopyrimidine repeat approximately 960 base pairs upstream from the human delta-globin gene. The binding site for the factor is within an unusual 250-base-pair domain that is greater than 95% pyrimidines on one strand. This domain is preferentially sensitive to S1 nuclease in supercoiled plasmids, indicating that it can adopt an alternative non-B-DNA conformation. A number of S1-sensitive sites within the domain, including the factor-binding site, have sequence characteristics associated with the formation of a triple helix (H-DNA). The position of the binding site between the fetal and adult beta-globin-like genes, its potential for adopting an unusual secondary structure, and the restricted activity of the binding factor to adult hematopoietic tissues suggest possible roles in hematopoietic cell development and hemoglobin switching.

Sulfhydryl substituents of the human erythrocyte hexose transport mechanism.

Sulfhydryl substituents of the hexose transport mechanism of human erythrocyte membranes were studied with membrane-impermeant and -permeant maleimide derivatives. Three sulfhydryl classes have been identified on the basis of their reactivity toward the reagents and their effects on the transport mechanism. Type I sulfhydryl is located at the outer (exofacial) surface of the membrane and bound covalently on treatment of intact cells with the membrane-impermeant glutathione-maleimide. This sulfhydryl is required for the transport, and it is protected from alkylation, i.e., its reactivity toward maleimides is decreased by the presence of D-glucose or cytochalasin B. Type II sulfhydryl is also required for the transport, but it differs from type I in that D-glucose (but not cytochalasin B) increases the reactivity toward maleimides. Further, it is located at the endofacial surface of the membrane, since reaction with glutathione-maleimide occurs only in leaky ghosts and not in intact cells. Alkylation by glutathione-maleimide of type I and type II sulfhydryls increases the half-saturation for the binding of D-glucose to erythrocyte membranes. In contrast, inactivation of type III sulfhydryls by N-ethylmaleimide or dipyridyl disulfide decreases the half-saturation concentration for the binding of D-glucose and other transported hexoses to the membranes; nontransported sugars are not affected similarly. Type III sulfhydryl is not inactivated by the polar reagent glutathione-maleimide and is probably located in a nonpolar domain of the transport mechanism. Inactivation of either type I or II sulfhydryls decreases or eliminates the flux asymmetry of the hexose transport mechanism.

Malignant ovarian germ cell tumors: a review of thirty-six cases.

Thirty-six patients with malignant ovarian germ cell tumors were treated between 1972 and 1983, including 16 with immature teratoma, five with endodermal sinus tumor, seven with dysgerminoma, and eight with mixed germ cell tumors. The median age at presentation was 18 years and mean primary tumor diameter was 18 cm. Twenty-five of the 27 patients who were treated with multiple-agent chemotherapy underwent second-look procedures, only two of which revealed persistent malignancy. No patients have developed recurrence after a negative second-look operation. Two of the three patients with failure of initial chemotherapeutic regimens had complete remissions with second regimens. Two patients have died of malignancy, one who presented with a Stage IA mixed germ cell tumor and one noncompliant patient with a Stage IA, grade 2 immature teratoma. The other 34 patients are alive without evidence of disease from 21 to 141 months, with a median follow-up of 68 months. These data confirm that multiple-agent chemotherapy has dramatically improved the prognosis for patients with malignant nondysgerminomatous ovarian germ cell tumors.

Influence of cholesterol content on red cell membrane viscoelasticity and fluidity.

The purpose of this investigation was to correlate the viscoelastic properties and lipid fluidity of the red blood cell membrane to its lipid composition. The viscoelastic properties of human red cells that had been enriched or depleted in cholesterol were determined by the micropipette technique. The lipid fluidity of the outer and inner leaflets of the erythrocyte membrane was concurrently assessed by steady state fluorescence depolarization. The elastic modulus and the viscosity moduli of the erythrocyte membrane showed no significant differences between the cholesterol-modified and the control cells. Cholesterol enrichment decreased the lipid fluidity of the outer membrane leaflet alone, and cholesterol depletion increased the fluidity mainly of the inner leaflet.

Lipid fluidity of the individual hemileaflets of human erythrocyte membranes.

The impermeant fluorescent probes (MIMAR reagents) described here permit the assessment of the lipid fluidity of individual membrane hemileaflets. They should also prove useful for examining the outer hemileaflets of the plasma membranes of intact cells. The observations, thus far, that normal human erythrocyte membranes have a characteristic asymmetry of fluidity, with the outer leaflet more fluid, correspond to prior findings with Mycoplasma, Newcastle Disease viral envelopes, and mouse LM cells. Hence, it is possible that the pattern is quite general in biological membranes. The particular lipid and protein components of the human-erythrocyte membrane that underly the fluidity asymmetry are unknown. The increased content of phosphatidylcholine in the outer leaflet and of the anionic phospholipids in the inner leaflet would be consonant with the fluidity difference. On the other hand, sphingomyelin, which tends to decrease fluidity, is localized mainly in the outer leaflet. Unknown at present is whether the cholesterol content of the two leaflets differs. From the results reported above, it is tempting to speculate that exogenously added cholesterol tends to localize in the outer leaflet, normally the more fluid leaflet, whereas endogenous cholesterol is more readily removed from the inner leaflet. This suggests, but clearly does not establish, that in the normal erythrocyte the cholesterol content of the inner leaflet exceeds that of the outer. Lastly, integral membrane proteins are expected to decrease lipid fluidity, and the usual pattern seen on freeze-fracture of large numbers of intra-membranous particles on the cytoplasmic face may signify a greater influence of protein in the inner leaflet. The hypothesis that perturbations of the fluidity of a given hemileaflet influence the membrane proteins (and their associated functions) in that leaflet is well-supported by the evidence described above. On the other hand, we understand less well the mechanisms by which lipid fluidity influences the proteins. For example, the decrease in sulfhydryl group reactivity of spectrin, actin, and Band 3 owing to cholesterol depletion (Table 7) may be due to a physical displacement of these proteins, as suggested by Borochov and Shinitzky. Why then does the reactivity of glyceraldehyde-phosphate dehydrogenase sulfhydryl groups increase under these conditions? There remains much to learn about membrane molecular mechanics and lipid-protein interactions. In such studies the impermeant MIMAR probes described here should prove useful.

Role of membrane lipids in cold agglutination of human erythrocytes.

The membrane lipid fluidity of normal human erythrocytes was modified by enrichment and depletion in cholesterol, and the expression of I and SP1 antigens was assayed by quantitative hemagglutination from 4 degrees to 24 degrees C by use of a continuous flow system. Below 16 degrees--18 degrees C, cholesterol enrichment increased and cholesterol depletion decreased percent agglutination. As temperatures approached approximately 18 degrees--20 degrees C, differences in agglutination between modified and unmodified erythrocytes became insignificant despite marked differences in lipid fluidity at that temperature. Thus, fluidity changes alone cannot be responsible for the effect of membrane cholesterol on cold agglutination. In an additional study, the temperature dependence of a relative equilibrium association constant, estimated by probit analysis of percent agglutination at various antisera concentrations, was biphasic with a sharp break at 16 degrees C. Our studies are consistent with the hypothesis that I and Sp1 antigens preferentially partition into a lipid domain that forms during lateral phase separation of membrane lipid developing at low temperature. A resulting increase in antigen density would then become responsible for augmented agglutination by specific antibody.

Acanthocytosis and cholesterol enrichment decrease lipid fluidity of only the outer human erythrocyte membrane leaflet.

The structure and functions of the human erythrocyte are influenced by the composition and organization of the membrane lipids. The outer (exofacial) and inner (endofacial) leaflets of the erythrocyte membrane differ in lipid composition, and recent studies using a group of membrane-impermeant pyrene fluorophores have demonstrated that the lipid fluidity of the outer leaflet exceeds that of the inner. Using one of these probes, pyrene butyryl hydrazide linked to the tetrasaccharide stachyose (SPBH), we have compared the lipid fluidity of the outer and inner leaflets in normal human erythrocytes treated experimentally to alter membrane cholesterol content and in acanthocytes, erythrocytes of altered morphology found in individuals with the genetic disorder abetalipoproteinaemia. The results, reported here, demonstrate that hemileaflet fluidity can be altered selectively: acanthocytosis and experimental cholesterol enrichment decrease the lipid fluidity of the outer but not the inner hemileaflet.

Pressure dependence of pyrene excimer fluorescence in human erythrocyte membranes.

The intensity of pyrene excimer fluorescence in human erythrocyte membranes and in sonicated dispersions of the membrane lipid (liposomes) was examined as a function of pressure (1-2080 bar) and temperature (5-40 degrees C). Higher pressure or lower temperature decreased the excimer/monomer intensity ratios. A thermotropic transition was detected in both membranes and liposomes by plots of the logarithm of the excimer/monomer intensity ratio versus 1/K. The transition temperature of the membranes was 19-21 degrees C at 1 bar and 28-31 degrees C at 450 bar, a shift with pressure of approx. 20-22 K per kbar. Corresponding transition temperatures of the liposomes were 21 degrees C at 1 bar and 33 degrees C at 450 bar, a shift of approx. 27 K per kbar. The observed pressure dependence of the thermotropic transition temperature is similar to that reported for phospholipid bilayers and greatly exceeds that of protein conformation changes. In concert with the liposome studies the results provide direct evidence for a lipid transition in the erythrocyte membrane.

Pulmonary hypertension and sudden death in aortic stenosis.

Sudden death is now an infrequent occurrence in severe aortic stenosis. However, an impressive increase in pulmonary arteriolar resistance has been found in some patients with end-stage aortic stenosis dying suddenly or deteriorating suddenly after catheterisation. Pulmonary hypertension does not seem to cause sudden death, but, in conjunction with decreased cardiac output, a critical reduction in aortic orifice area, and left ventricular failure, pulmonary hypertension identifies a population at significant risk. The rare finding of severe pulmonary hypertension in aortic stenosis should be considered an important marker for sudden death and in association with left ventricular failure may indicate an urgent need for valve replacement, regardless of the apparent clinical condition of the patient. In a small number of subjects catheterised postoperatively, increased pulmonary arteriolar resistance lessened rapidly.