Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen.

The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal controls (P < 0.001, P = 0.044 respectively), and higher VEGFp, but not VEGFs, than patients with benign disease (P = 0.009) and patients with localized disease (P = 0.004). However, the highest VEGFp and VEGFs concentrations were seen in patients in remission compared with normal controls (P < 0.001 and P = 0.008, respectively). VEGFp concentrations in patients in remission were also higher than in patients with benign disease (P = 0.01) or patients with localized disease (P = 0.005). Tamoxifen treatment was significantly associated with higher circulating and platelet-derived VEGF levels. Circulating VEGF did not correlate with any clinicopathological factor, including MVD or VEGF expression. VEGF expression was significantly correlated with estrogen receptor status and inversely correlated with tumor grade. MVD correlated with tumor size. Tamoxifen-induced increases in VEGF may be important in clinical prognosis or associated pathologies.

Serum beta 2-microglobulin and human immunodeficiency virus infection.

Serum beta 2-microglobulin (beta 2-M) was measured in two prospectively evaluated groups of homosexual men in 1983 and 1985. Serum beta 2-M was raised in 64% of patients with HIV infection, but in only 6.7% of uninfected homosexuals. Depression of the total lymphocyte count was only clinically useful when it reached less than 1.0 X 10(9)/l. In further studies all patients with AIDS and AIDS-related complex (ARC) had raised levels of serum beta 2-M. Mean levels of beta 2-M did not differ between patients with persistent generalized lymphadenopathy (PGL) and asymptomatic HIV-infected patients. Raised serum levels of beta 2-M accompanied major immune dysfunction in HIV infection. Serum beta 2-M levels of greater than 3.0 mg/l in HIV-infected homosexual men were associated with progression to AIDS.

Serum alpha-thiol protease inhibitor concentrations in health and disease.

Serum alpha-thiol protease inhibitor (alpha-TPI) concentration was assayed by radial immunodiffusion in normal subjects, pregnant women, and in a wide variety of diseases. The normal concentration (448 (SD 75) mg/l) increased significantly (p less than 0.001) in pregnancy to 575 (89) mg/l, and in prostatic cancer treated by oestrogens to 666 (87) mg/l. Inconsistent changes were observed in inflammatory and malignant disease and in liver disease. A temporary pronounced fall of alpha-TPI was seen after burn injury, and a sustained fall after bone marrow transplantation. Crossed immunoelectrophoresis showed that the serum alpha-TPI occurred in two forms, with alpha 2 and alpha 1 electrophoretic mobilities. A heavy demand on this antiprotease may result in suppression of the alpha 1 form.

Serum beta 2-microglobulin and C reactive protein concentrations in viral infections.

Serum beta 2-microglobulin concentrations were assayed in a number of virus diseases. Infectious mononucleosis, cytomegalovirus, and influenza A were associated with pronounced increases in serum beta 2-microglobulin concentration. Smaller increases, with values generally less than 4 mg/l, were noted in other viral infections. Apart from in acute influenza A, the C reactive protein and beta 2-microglobulin responses were not associated.

Alpha-1-microglobulin: an indicator protein for renal tubular function.

A comparison of urinary alpha 1-microglobulin concentrations to the behaviour of other indicators of renal tubular disorders, beta 2-microglobulin, retinol-binding protein and N-acetyl-beta-D-glucosaminidase (NAG) has been made. In acute tubular disorders the concentrations of urinary beta 2M and RBP are highly correlated (r = 0.89) but this is less marked for alpha 1M and beta 2M (r = 0.55) and alpha 1M and RBP r = 0.48. NAG tends to run a parallel course to alpha 1M concentrations but lags behind the recovery of low molecular weight protein reabsorption following injury of the tubular cells. The concentrations of alpha 1M, and in particular its stability at low pH suggest that this protein may be useful in screening for tubular abnormalities and detecting chronic asymptomatic renal tubular dysfunction. Urinary alpha 1M greater than 15 mg/g creatinine is strongly suspicious of a proximal tubular dysfunction. The distinction between pure tubular proteinuria and mixed glomerular and tubular proteinuria requires further analysis.

Changes in plasma beta 2 microglobulin concentrations after allogeneic bone marrow transplantation.

Plasma concentrations of beta 2 microglobulin (B2M), the light chain of the class I major histocompatibility complex, were measured serially in 26 patients undergoing allogeneic bone marrow transplantation (BMT). The concentrations fell after conditioning treatment, and recovered when the marrow was transplanted. Bacterial infection did not influence B2M concentration, but nine of 22 episodes of acute graft versus host disease were associated with raised concentrations. Increased plasma B2M concentrations were also a feature of eight episodes of chronic graft versus host disease, and these fell after treatment. Reactivation of herpes simplex, varicella zoster, or cytomegalovirus infections were also accompanied by raised B2M concentrations. Three patients with cytomegalovirus pneumonitis had high concentrations of plasma B2M, the rise starting between five and 22 days before onset of symptoms. Although it is non-specific, serial measurement of plasma B2M in patients undergoing BMT may be clinically useful in monitoring chronic graft versus host disease.

Proximal renal tubular function in myelomatosis: observations in the fourth Medical Research Council trial.

Proximal renal tubular function was studied in 522 consecutive patients entered into the Medical Research Council's fourth myelomatosis trial. Assessment was made at presentation after a 48 h period of hydration but before administration of chemotherapy. The most common abnormalities in the urine other than light chain proteinuria were raised concentrations of the low molecular weight proteins alpha 1-microglobulin and alpha 1-acid glycoprotein. These were usually accompanied by increases in urinary beta-N-acetyl-D-glucosaminidase concentrations. The concentration of these substances in the urine directly correlated with urinary free light chain output. This tubular proteinuria was seen whether or not patients had impaired glomerular function, as assessed by a rise in serum creatinine concentration. Urinary concentrations of retinol binding protein, however, were generally increased only when serum creatinine concentrations were raised. This applied even when there were high concentrations of light chains, alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase in the urine. There is therefore a selective tubular proteinuria in myelomatosis which is seen in almost all patients with urinary light chain values greater than 1 u/l. This proteinuria is generally reversible, when light chains no longer appear in the urine. Patients whose serum creatinine was greater than 200 mumol/l, however, had increased urinary output of retinol binding protein in addition to increased excretion of alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase. Tubular proteinuria in many of these patients presenting in renal failure persisted even when light chain output was reduced after chemotherapy.

A method to detect the in vitro modification of serum beta-2-microglobulin in health and disease.

The electrophoretically fast moving form of beta-2-microglobulin (alpha-B2m) was shown by crossed immunoelectrophoresis to be produced in vitro after incubation at room temperature and was not present in freshly drawn sera. A radioisotopic assay was developed to measure this conversion to alpha-B2m in sera from 14 healthy individuals and from 208 patients with benign and malignant disease. The activity was present in all the sera tested and the levels were significantly higher in sera from patients with small cell lung cancer, prostate cancer and in childhood lymphomas when compared to the level in normal sera.

Serum bone alkaline phosphatase and CA 549 in breast cancer with bone metastases.

A monoclonal radioimmunometric assay for bone alkaline phosphatase (BAP) developed by Hybritech, USA, with an upper limit of normal of 40 U/l, was examined in 125 patients with breast cancer. Eleven patients who remained tumour free for 5-6 years had small intra-individual variations of BAP. The median value in 33 patients with multiple bone metastases of 60 U/l was elevated when compared with that in 40 patients with no evidence of metastases (22 U/l) and 34 U/l in 16 with limited bone disease (1-2 hot spots). By contrast, only 2 out of 25 patients with extensive local recurrence, lung, or hepatic metastases, without bone involvement showed an increase of BAP (< 200 U/l). The BAP levels were compared to total alkaline phosphatase (TAP), the breast cancer marker CA 549 (HybriBREScan). Longitudinal studies of 15 patients with bony metastases showed that TAP and BAP were well correlated only when the TAP was elevated; CA 549 and BAP could vary independently. The main use of BAP in patients with bone metastases appears to be an aid to the monitoring of treatment; however, it is not significantly raised in limited bone metastases.

Bone alkaline phosphatase in rheumatic diseases.

A double monoclonal immunoradiometric assay specific for bone alkaline phosphatase (BAP) was used to determine whether the raised total alkaline phosphatase (TAP) often found in patients with active rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is derived from bone or liver. Fifty-eight patients with RA were compared to 14 with AS and 14 with non-inflammatory rheumatic diseases (NI). None had clinical liver disease and only one had a slightly elevated aspartate transaminase activity. Elevated BAP concentrations were found in seven patients (5 RA, 1 AS, 1 NI), only two of whom also had abnormal TAP. Abnormal TAP activities were found in only three patients (all RA). BAP did not correlate with disease activity in RA or AS. In contrast, TAP correlated with disease activity (assessed by plasma viscosity) in RA (P < 0.002) and gamma-glutamyl transferase (GGT) also correlated with plasma viscosity in RA (P < 0.01). Both TAP and BAP were significantly correlated with GGT in RA (P < 0.001 and P < 0.02, respectively). These findings are discussed, together with possible reasons for the conflicting nature of some of the observations.

Hope in the older adult with chronic illness: a comparison of tow research methods in theory building.

When current theory about a concept of interest is insufficient, the researcher may desire to build or expand theory. Two research methods for building nursing theory are compared by asking the same question using each method. Phenomenology was used to analyze the interviews of six older adults with chronic illness regarding their experience of hope. Eight theme categories depicted the essential structure. Using concept mapping, eight older adults with chronic illness generated statements about hope. Nine clusters resulted. The methods are compared for procedure and outcome. Although differing with regard to time and participant involvement, the similarity of outcomes suggests that qualitative research is robust.

Epidemiology of Haemophilus influenzae invasive disease in Jamaica, 1990-1993.

Haemophilus influenzae (H influenzae) invasive disease was studied retrospectively over a four-year period in children admitted to the Bustamante Hospital for Children in Kingston, Jamaica. A total of 86 cases were identified. The mean estimated annual incidence of H influenzae invasive disease in Kingston and St Andrew was 39 per 100,000 children under 5 years of age. The majority (77%) of cases were in the under 2-year age group. A distinct seasonal pattern was noted, with a significantly higher proportion of patients (57-73%) presenting in the cooler months. Meningitis was the most common clinical diagnosis, accounting for 76% of the cases. Poor outcome was demonstrated in 21.5% of patients with meningitis. Sensitivity testing of H influenzae isolates revealed a resistance rate of 26% for ampicillin and 7% for chloramphenicol. The epidemiological findings in this study provide reasonable guidelines for empiric antibiotic therapy and also support the need to seriously consider vaccine prophylaxis in Jamaican children.

The practice of professional nurse case management.

Professional Nurse Case Management began at Carondelet St. Mary's Hospital 13 years ago with a goal of delivering direct nursing services to high-risk chronically ill clients in the community. Nurse case management has evolved as the healthcare delivery environment has changed. This study revisits this well-described model and assesses the impact of managed care on the practice of professional nurse case management. Concept mapping was used to describe the current practice of nurse case management at Carondelet Health Network. Professional nurse case managers modeled their practice as a series of concentric spheres, each subsuming the spheres within it. Moving from the outside to the core, the spheres represent developmental framework; practicing the Carondelet mission; group practice; integration, education, and acculturation of clients within the health system; and client-focused therapeutic relationship. One final sphere of practice, bridging the gaps, represented actions that cross all spheres of nurse case management.

Use of mucin like cancer associated antigen (MCA) in the management of breast cancer.

A study of the epithelial mucin marker MCA was made in 233 patients with breast cancer. Only 6% of 72 patients with Stage I-III disease had a raised MCA (greater than 15 U ml-1) when assessed following surgical treatment of the primary tumour. Raised levels of MCA occurred in one out of 20 (10%) patients with stable local recurrence, and six out of ten (60%) patients with progressive local recurrence. In 115 patients with metastases 89 (77%) had a raised MCA, tumour extent and disease activity both influenced the MCA level. The change of MCA level during the treatment of 11 cases of local recurrence and 55 cases of metastatic disease showed a 64 and 84% concordance respectively with the change in clinical status. Coincidental measurement of MCA and bone scans showed a raised MCA in one out of 63 (1.5%) patients with negative or equivocal scans, and 26 out of 35 (74%) with positive scans. MCA provides a useful marker for the monitoring of the treatment of local recurrence and metastatic disease, and an independent indicator of the effects of changes in treatment.

Tubular dysfunction and microalbuminuria in insulin dependent diabetes.

The nature of microproteinuria in the early years of insulin-dependent diabetes was investigated in a cross sectional study of 80 children with insulin-dependent diabetes and 40 normal children. Urinary excretion of three low molecular weight proteins: alpha-1-microglobulin, beta-2-microglobulin and kappa light chains was used as an index of proximal renal tubular function. The first urine samples of the morning were collected and excretion of proteins measured was expressed as ratio of protein to creatinine. There was a strong correlation between excretion of alpha-1-microglobulin and chi light chains and their excretion was significantly higher in diabetic children indicating decreased proximal tubular reabsorbtion. The excretion of beta-2-microglobulin was found to be an unsatisfactory index of proximal tubular function. Urinary albumin excretion was not significantly raised in diabetic children and did not correlate with urinary alpha-1-microglobulin or chi light chain excretion. Glycaemic control might influence proximal tubular function as both urinary glucose concentration and glycosylated haemoglobin showed correlations with urinary alpha-1-microglobulin excretion and with urinary chi light chain excretion.

Plasma beta-2-microglobulin and fibronectin levels in beta-thalassaemia.

The plasma beta 2-microglobulin (beta 2-MG) levels in 118 children with thalassaemia were investigated. The mean level was higher than in healthy children. A significant increase of beta 2-MG was associated with hypersplenism (3.14 +/- 0.6 mg/l). The beta 2-MG levels appeared to reflect reticuloendothelial system activity but were not related to iron overload. Fibronectin levels were generally lower than in healthy adults; profound chronic fibronectin depletion was not accompanied by an increased liability to infection.