Patient Involvement: A New Source of Stress in Health Care Work?

Patients have become increasingly well informed with higher expectations to be involved in decision-making processes regarding their care and treatment. However, few studies have examined the impact of patient involvement on health care providers’ partnership-building communication. The aim of this study was to measure and explore the self-reported effects of patient involvement on the work of physicians and nurses. A questionnaire survey was distributed among cardiology staff in 12 Swedish hospitals (N = 488, response rate 67%). The sample was comprised of registered nurses (RNs, n = 303), licensed practical nurses (LPNs, n = 132), and physicians (MDs, n = 53). Confirmatory factor analysis was used to examine seven questionnaire statements concerning implications of patient involvement for one’s clinical work. Regression analyses were used to examine factors associated with staff’s partnership-building communication. Analysis confirmed two distinct factors accounting for 57% of the total variance, representing both negative—“Hassles”—and positive—“Uplifts”—aspects of patient involvement. Regression analyses revealed that only positive aspects (i.e., uplifts) of patient involvement predicted staff behavior aimed at involving patients. Working with actively involved patients may be a source of stress, both negative and positive, for health care professionals. By developing work routines for involving patients in their care, health care workplaces may help health care professionals to buffer the negative effects, and enhance the positive effects, of that stress.     

Is 18F-FDG PET/CT useful for imaging and management of patients with suspected occult recurrence of cancer?

Rising serum tumor markers may be associated with negative imaging in the presence of cancer. CT and (18)F-FDG PET may yield incongruent results in the assessment of tumor recurrence. The present study evaluates the incremental role of (18)F-FDG PET/CT for the diagnosis and management of cancer patients with increasing levels of tumor markers as the sole indicator of potential recurrence after initial successful treatment. METHODS: Thirty-six cancer patients with increasing levels of tumor markers during follow-up and negative CT underwent (18)F-FDG PET/CT, which showed 111 sites of increased tracer uptake. PET/CT was compared with PET results on a site-based analysis for characterization of (18)F-FDG foci and on a patient-based analysis for diagnosis of recurrence. The clinical impact of PET/CT on further patient management was evaluated. RESULTS: Thirty patients (83%) had recurrence in 85 malignant sites (77%). For the site-based analysis, PET had a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 96%, 50%, 85%, 85%, and 82%, respectively, as compared with the performance indices of PET/CT of 100%, 89%, 97%, 97%, and 100%, respectively. There was a statistically significant difference between the specificity (P < 0.05) and accuracy (P < 0.001) of PET and PET/CT for precise characterization of suspected lesions. For the patient-based analysis, PET had a sensitivity, specificity, and accuracy of 93%, 50%, and 86%, respectively, as compared with PET/CT with values of 93%, 67%, and 89%, respectively (P = not significant). PET/CT was the single modality that directed further management and treatment planning in 12 patients (33%). CONCLUSION: The results of this study indicate that PET/CT may improve the accuracy of occult cancer detection and further lead to management changes in patients with increasing levels of tumor markers as the sole suspicion of recurrent malignancy.     

Deficiency of P-selectin in a patient with grey platelet syndrome

Abstract: Patient B.G. is a 29-yr-old female with a lifelong bleeding disorder characterized clinically by a highly increased bleeding time, menorrhagias, long-lasting bleeding after cuts and tooth extractions and large post-traumatic haematomas. Her coagulation tests were within normal range, platelet count was 140,000–160,000 per μl, but platelet function was impaired as demonstrated by the absence of collagen-induced aggregation, although no abnormalities were detected in aggregation response to ADP and ristocetin. Morphologically her platelets were characterized by gigantic size – average profile area was about 2.5 times higher than that of control donors, and severe deficiency of α-granules – only 16% of their number in control donors. These features taken together indicated the diagnosis of grey platelet syndrome. As has been shown by quantitative immunoblotting, patient's platelets contained small amounts of α-granule membrane protein P-selectin – about 15% of that in control donors. The content of plasma membrane glycoproteins IIb–IIIa and Ib was not reduced, suggesting the specific deficiency of α-granule membrane protein. Thus, B.G. is the second patient described in the literature (see also Lages et al, J Clin Invest 1991: 87: 919–929) with combined deficiency of α-granules and P-selectin.     

L-thyroxine increases susceptibility of adult rats to low K+-induced ventricular fibrillation, and sinus rhythm restoration in old rats

Hypokalaemia increases the risk for life-threatening arrhythmias; however, data about interaction with thyroid status are lacking. The aim of this study was to investigate vulnerability of l-thyroxine (T(4))-treated adult and old rats to low K(+)-induced ventricular fibrillation (VF) as well as the ability of the heart to recover sinus rhythm. The experiments were performed on isolated heart preparations using the heart of 4- and 20-month-old female Wistar rats without and with feeding with T(4) 50 microg (100 g day)(-1) over a period of 2 weeks. Perfusion of the isolated heart with oxygenated Krebs-Henseleit solution at constant pressure was followed by perfusion with K(+)-deficient solution until occurrence of VF (< 10 min). After 2 min of sustained VF, the heart was perfused with normal solution for 10 min, during which sinus rhythm was restored. ECG, left ventricular pressure (LVP) and coronary flow were continuously monitored. The results showed that compared with untreated rats, the onset of low K(+)-induced ventricular premature beats was delayed and their number was significantly decreased in both T(4)-treated groups. Nevertheless, VF occurred earlier in T(4)-treated than in non-treated adult rats (6.78 +/- 0.28 vs. 9.59 +/- 0.55 min, P < 0.05), whereas the difference was not significant in aged animals. Furthermore, sinus rhythm appeared earlier in old T(4)-treated rats compared with non-treated rats (7.18 +/- 0.57 vs. 8.94 +/- 0.64 min, P < 0.05), whereas in adult hearts it set in at practically the same time regardless of treatment. In conclusion, our results indicate that administration of a pharmacological dose of T(4) can increase the risk of low K(+)-induced VF in adult but not in old animals; in the latter it even facilitated restoration of sinus rhythm. Moreover, enhanced mechanical function was observed in both adult and old T(4)-treated hearts.     

Production of herpes B virus recombinant glycoproteins and evaluation of their diagnostic potential

B virus (cercopithecine herpesvirus 1) is the only deadly alphaherpesvirus that is zoonotically transmissible from macaques to humans. The detection of humoral immune responses is the method of choice for the rapid identification of B virus-infected animals. We evaluated the diagnostic potential of recombinant B virus glycoproteins for the detection of immunoglobulin G (IgG) antibodies in monkey and human sera. Glycoproteins B, C, and E and secreted (sgG) and membrane-associated (mgG) segments of glycoprotein G (gG) were expressed in the baculovirus expression system, while gD was expressed in CHO cells. We developed recombinant protein-based IgG enzyme-linked immunosorbent assays (ELISAs) and compared their diagnostic efficacies by using B virus antibody-negative (n = 40) and -positive (n = 75) macaque sera identified by a whole antigen-based ELISA and Western blotting. The diagnostic sensitivities of the gB-, gC-, gD-, and mgG-ELISAs were 100, 97.3, 88.0, and 80.0%, respectively. The specificities of the gB-, gC-, and gD-ELISAs and of the mgG-ELISA were 100 and 97.5%, respectively. In contrast, the sensitivities and specificities of sgG- and gE-ELISAs were low, suggesting that sgG and gE are less effective diagnostic antigens. Sera from nonmacaque monkeys cross-reacted with gB, gC, and gD, and only baboon sera reacted weakly with mgG. Human herpes simplex virus type 1 (HSV-1)- and HSV-2-positive sera pools reacted with gB and gD, whereas sera from B virus-infected individuals reacted with all four antigens. These data indicate that gB, gC, gD, and mgG have a high diagnostic potential for B virus serodiagnosis in macaques, whereas mgG may be a valuable antigen for discrimination between antibodies induced by B virus and those induced by other, closely related alphaherpesviruses, including HSV-1 and -2.     

Single-step nested polymerase chain reaction for detection of different genotypes of hepatitis C virus

Hepatitis C virus (HCV) exhibits considerable sequence variability and circulates in the blood at extremely low levels. Current methods for detecting HCV RNA are based mostly on nested polymerase chain reaction (PCR), in which part of the first amplification product is reamplified in the second tube by an internal primer pair. A novel nested PCR method was developed in which the two successive amplification processes are carried out in the same tube with a single step of physical manipulation. Careful selection of highly conserved sequences of the 5′ noncoding region as primers enabled successful detection of all three major genotypes circulating in France, including the one with variation in this region. Retaining high sensitivity of the conventional nested PCR, the novel method reduced greatly the risk of carry-over contaminations. It was also cost- and time-saving. The one-step nested PCR method is especially suitable for routine diagnosis of HCV infection in clinical laboratories. © 1995 Wiley-Liss, Inc.     

Isolation and characterization of human smooth muscle cells from umbilical cord vein and their reconstitution in a vascular co-culture model with underlying endothelial cells

Smooth muscle cells have been isolated from human umbilical cord veins, characterized and cultured for the development of an endothelialsmooth muscle cell co-culture system. After harvesting endothelial cells, the umbilical cords were trimmed of amnion, connective tissue and arteries, split into pieces, cut open longitudinally and placed with the luminal surface of the explant down onto a culture plate, without the use of proteolytic enzymes. Adherent primary cells were sequentially passaged and various cytological/biochemical characterizations were performed between passages 2 and 10. Cells stained positive for antibodies against smooth muscle actin, negative for antibodies against factor VIII and displayed typical hill and valley morphology when confluent. Cell proliferation was stimulated and supported in a concentration-dependent manner by both human serum and fetal bovine serum over the range 1%–20%. The use of human serum at concentrations >10% decreased the population doubling time during exponential growth by circa 50%. The cells were also characterized by high seeding efficiencies (>70%) and retained their diploid karyotype for up to 3 months in culture. Endothelial cells and smooth muscle cells prepared from umbilical veins were then seeded at varying densities onto either side of porous tissue culture inserts coated with fibronectin. Utilising the measurement of electrical resistance, the optimal seeding density of 5×10⁴ cells/cm² for each cell type gave maximal resistance across the cell bi-layer already after 24 hours, which remaining essentially unaltered for up to 4 days of culture and which was always substantially higher than the resistance of filters seeded only with endothelial cells on one side. This was not substantially affected either by increasing passage of the HUVSM cells cultured with a fixed passage of endothelial cells, or by varying the donor origin of the endothelial cells. In terms of functionality of the selective permeability of the model, the calcium ionophore ionomycin (25 M), added to the endothelial side of the bi-layer, caused a 30% reduction in the electrical resistance across the co-culture within 60 minutes, with control resistance being re-established within 1 hour of removal of the ionophore by washing. These results clearly indicate that smooth muscle cells and endothelial cells prepared from the same human blood vessel can be reconstituted into a functional vascular model suitable for the study of biochemical, physiological and toxicological phenomena in the human vascular wall.Abbreviations BCA bicinchoninic acid - BSA bovine serum albumin - DMEM DMEM medium supplemented with 4.5 g/l glucose, 100 IU/ml penicillin, 100 g/ml streptomycin and 1.25 g/ml fungizone - DMEM-1 DMEM supplemented with 20% FBS, 300 IU/ml penicillin, 300 g/ml streptomycin and 3.75 mg/ml fungizone - DMEM-2 DMEM supplemented with 20% FBS, 100 IU/ml of penicillin, 100 g/ml of streptomycin and 1.25 g/ml of fungizone - DMSO dimethyl sulfoxide - FBS fetal bovine serum - HPF human pulmonary fibroblasts - HS human serum - HUVE human umbilical vein endothelial - HUVSM human umbilical vein smooth muscle - M199 M199 medium supplemented with 20% HS, 100 IU/ml penicillin, 100 g/ml streptomycin, 1.25 g/ml fungizone and 2 mM L-glutamine - P passage number - PBS phosphate buffered saline - TCA trichloroacetic acid - vwF von Willebrand factor (factor VIII)     

Finding genes for SLE: complex interactions and complex populations

Many years of work, multiplex family collection and endless genotyping finally give fruit. The original aim cannot be lost. The aim is not only to identify mutations involved in susceptibility for systemic lupus erythematosus (SLE) but to elucidate the disease pathogenesis as well. After genetics comes the biology. We review our recent findings on the genetics of lupus, provide possible mechanisms for disease susceptibility and present some facts on the problematic of identifying susceptibility mutations for complex diseases in complex human populations.     

Pre-exposure of murine macrophages to lipopolysaccharide inhibits the induction of nitric oxide synthase and reduces leishmanicidal activity

Murine macrophages produce nitric oxide (NO) from L-arginine on stimulation with lipopolysaccharide (LPS), alone or with interferon-γ (IFN-γ). The effect of incubation of macrophages with low concentrations of LPS on NO synthesis on subsequent stimulation was investigated, using a murine macrophage cell line, J774, and peritoneal macrophages from CBA mice. Cells which had been incubated with LPS produced significantly lower amounts of NO, and expressed lower levels of NO synthase activity, following stimulation with IFN-γ and LPS, or with a high concentration of LPS. This effect was not reversed by tumor necrosis factor-α. The ability of CBA macrophages to kill the intracellular parasite Leishmania major was markedly reduced by pre-incubation with LPS. Reduced NO production by macrophages previously exposed to LPS is a manifestation of endotoxin tolerance, and may represent an important means of regulation of NO synthesis and thus a survival mechanism for intracellular parasites.