Effects of exercise on transmitral gradient and pulmonary artery pressure in patients with mitral stenosis or a prosthetic mitral valve: a Doppler echocardiographic study

Doppler echocardiography was used to determine changes in transmitral gradient and pulmonary artery pressure after exercise in 12 patients with mitral stenosis and 11 patients with a prosthetic mitral valve. The mean transmitral gradient in the mitral stenosis group was 9 +/- 7 mm Hg at rest and increased to 17 +/- 8 mm Hg after exercise. In patients with a prosthetic mitral valve, exercise resulted in an increase in mean transmitral gradient from 5 +/- 2 to 8 +/- 3 mm Hg. Calculated pulmonary artery systolic pressure increased with exercise from 41 +/- 19 to 70 +/- 32 mm Hg in the mitral stenosis group and from 28 +/- 8 to 39 +/- 15 mm Hg in patients with a prosthetic valve. Exercise Doppler echocardiographic evaluation of changes in transmitral gradient and pulmonary artery systolic pressure was found to be technically simple and an important addition to the noninvasive evaluation of patients with mitral valve disease.     

The site‐specific epidemiology of hip fracture in the Australian Capital Territory with projections for the first half of the 21st century: Implications for clinical management and health services planning

Objectives: To analyse the site‐specific epidemiology of hip fracture (HF) for the ACT and to project HF up to 2051. Methods: Age‐ and sex‐specific rates of HF and projections of the number of HFs were calculated by applying the age‐ and sex‐specific rates to the median population projections. Results: Analysis of patterns of HF by anatomical site of fracture revealed a diverse relationship according to age and sex. Fracture rates were higher in men before age 60 (1.8 : 1), and thereafter in women (3.1 : 1). In the age group of 60–64 years, the female : male ratio was 8.2 : 1 for cervical versus 1.8 : 1 for trochanteric fractures. Treatment for osteoporosis was under‐utilised. HF in people aged > 60 years will almost double by 2011, and increase 2.5‐fold and 5.4‐fold by the years 2021 and 2051, respectively. The greatest increase will occur in older men. Conclusions: The number of HFs in the first half of the 21st century will increase dramatically. Aetiological and pathophysiological differences in HF emphasise the need to individualise preventative strategies.     

Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(- )-inhibitor complexes in sepsis

Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(- )-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(- 4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.     

Antibodies reactive with human T cell leukemia viruses in the serum of hemophiliacs receiving factor VIII concentrate

The third member of the family of T cell leukemia viruses (HTLV III) has been proposed as the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia, particularly those with factor VIII deficiency who receive commercial clotting factor concentrates. In a prevalence survey conducted between September 1982 and April 1984, initial serum samples from 74% of hemophiliacs who had ever been treated with commercial factor VIII concentrate, 90% of those frequently treated with factor VIII concentrate, and 50% of those treated with both factor VIII and factor IX concentrates had antibodies reactive against antigens of HTLV III, compared with none of the hemophiliacs treated only with factor IX concentrate or volunteer donor plasma or cryoprecipitate. Two of the seropositive patients have developed AIDS-related illnesses, and a third patient died of bacterial pneumonia. One initially seronegative patient developed antibodies against HTLV III during the study and is currently well. The predominant antibody specificities appear directed against p24 and p41, the presumed core and envelope antigens of HTLV III, suggesting that factor VIII concentrate may transmit the p24 and p41 antigens of HTLV III. However, the presence of infectious retroviruses in clotting factor concentrates and the effectiveness of screening and viral neutralization procedures remain to be determined.     

An important role for the alpha 1,3 fucosyltransferase, FucT-VII, in leukocyte adhesion to E-selectin

E-selectin is an adhesion molecule expressed on the surface of activated endothelial cells, which has been shown to be important in the initial steps of leukocyte extravasation into inflamed tissues. E- selectin binds neutrophils, monocytes, eosinophils, basophils, natural killer (NK) cells, and subsets of lymphocytes, although the precise ligand(s) on these cells have not been identified. Several studies have proposed certain carbohydrate structures, including sLex and related structures, as E-selectin ligands. In contrast to these studies, we report here the identification of several human B cell lines that exhibit binding to E-selectin without expression of any of the previously identified E-selectin binding carbohydrate epitopes. The unique carbohydrate phenotype of these B cell lines suggests that they may express a novel, sialylated carbohydrate structure(s) that binds to E-selectin. To investigate the enzymatic basis of this novel form of E- selectin binding, we examined the expression of the two principal leukocyte alpha 1,3 fucosyltransferases, FucT-IV and FucT-VII, in a panel of human hematopoietic cell lines. FucT-VII was expressed in all E-selectin binding cell lines except one, whereas FucT-IV was expressed by nearly all cell lines, regardless of their ability to bind E- selectin. In addition, transfection of cells with cDNA encoding FucT- VII conferred E-selectin binding ability. Taken together, these data suggest that, regardless of surface carbohydrate phenotype, E-selectin binding ability is determined largely by expression of FucT-VII.     

Eosinophils do respond to fMLP

Eosinophils were isolated from normal human blood by separation over Percoll gradients, which resulted in eosinophil suspensions of a purity higher than 95% and recoveries of about 65%. Normal human eosinophils were found to respond to formyl-methionyl-leucyl-phenylalanine (fMLP) at concentrations greater than 10(-7) mol/L with an increase in the concentration of intracellular free calcium, oxygen consumption, nitroblue tetrazolium reduction, and chemiluminescence. The maximal response of eosinophils to fMLP was lower than that of neutrophils isolated from the same blood samples and required at least ten times as much fMLP as was needed for neutrophils. Low fMLP concentrations (approximately 10(-8) mol/L), which in themselves did not stimulate O2 consumption by either eosinophils or neutrophils, primed these cells to respond to a suboptimal concentration of another stimulus. Purification of eosinophils after treatment of whole blood with fMLP showed that these eosinophils had lost their ability to respond to fMLP. We conclude that normal eosinophils do respond to fMLP and that therefore fMLP should not be used to isolate eosinophils.     

Purification and characterization of a human T-lymphocyte-derived granulocyte-macrophage colony-stimulating factor

We have examined the biologic and physical properties of a human T- lymphocyte granulocyte-macrophage colony-stimulating factor (CSF). The source of the factor is a T-lymphoblast cell line (Mo) that was derived from a patient with a T-cell variant of hairy-cell leukemia. The Mo line constitutively produces a number of lymphokines that are normally produced by mitogen-stimulated T lymphocytes. Medium conditioned by Mo cells grown in the absence of serum is especially rich in CSF activity, and using this source we have purified the CSF to a specific activity of about 3.5 x 10(6) colonies per 10(5) Ficoll-Hypaque-separated human bone marrow cells plated per mg protein. The Mo CSF stimulates the formation of both granulocyte and macrophage colonies in vitro (in about equal numbers) and it has a relatively steep dose-response curve. Both the crude and purified preparations stimulated the formation of eosinophil as well as neutrophil colonies; it is unclear whether this is due to the presence of multiple factors with similar physical properties or a single factor with multiple activities. The CSF has little stimulating activity for mouse bone marrow progenitors. Physically, the Mo CSF is an acidic glycoprotein of molecular weight about 34,000. It binds to concanavalin A-Sepharose, is unusually resistant to denaturing agents and heat treatment, and is not inactivated in the presence of sulfhydryl reagents. The Mo CSF is distinct from factors stimulating erythroid colony formation and inhibiting neutrophil migration that are also produced by Mo cells. It differs in several physical and biologic properties from other human CSFs that have been characterized.     

Direct cost of rheumatoid arthritis during the first six years: a cost- of-illness study

The objective was to estimate the annual direct disease-related cost of rheumatoid arthritis (RA) during the first 6 yr and to determine which socio-demographic and clinical characteristics relate to these costs. The study population consisted of 424 RA patients who had participated in a (population-based) trial on therapeutic strategies for early RA since 1990 and were not lost to follow-up in April 1996. A questionnaire on costs due to RA was sent to these patients; 363 (86%) completed questionnaires were analysed. The total annual direct cost per patient was estimated by adding up the costs of health care workers, days admitted to care facilities, medication, monitoring for side-effects, alternative medicine, adaptations in the home, devices, and other direct costs such as travelling expenses. The mean annual direct cost due to RA was estimated to be Dfl. 11,550 per patient. An obvious increase in direct cost with increasing disease duration was not found. Patients with higher disease activity exhibited significantly higher costs compared to patients with lower disease activity. A multiple logistic regression model showed that greater disability and lower age increased the odds for high costs. The annual direct cost of RA averaged out at Dfl. 11,550 per patient (i.e. Pound Sterling 3680). A high total direct cost in the first 6 yr of disease is related to severe functional disability and lower age.