Prevalence and predictors of airflow obstruction in an HIV tertiary care clinic in Montreal, Canada: a cross-sectional study.

OBJECTIVES: The reported prevalence of chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWHIV) varies widely. Our objective was to estimate the prevalence of airflow obstruction and COPD in unselected PLWHIV and identify characteristics that increase the risk of nonreversible airflow obstruction in order to guide case finding strategies for COPD. METHODS: All adults attending the Chronic Viral Illness Service were invited to participate in the study, regardless of smoking status or history of known COPD/asthma. Individuals underwent spirometric testing both before and after use of a salbutamol bronchodilator. Airflow obstruction was defined as forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) < 0.7 post-bronchodilation, whereas COPD was defined as FEV1 /FVC < 0.7 post-bronchodilation and Medical Research Council (MRC) score > 2. Multivariate logistic regression was used to evaluate risk factors associated with airflow obstruction, reported as adjusted odds ratios (aORs). RESULTS: Five hundred and three participants successfully completed spirometry testing. The median (Q1; Q3) age was 52 (44; 58) years. The median (Q1; Q3) CD4 count was 598 (438; 784) cells/µL and the median (Q1; Q3) nadir CD4 count was 224 (121; 351) cells/µL. There were 119 (24%) current smokers and 145 (29%) former smokers. Among those screened, 54 (11%) had airflow obstruction whereas three (1%) of the participants had COPD. Factors that were associated with airflow obstruction included a history of smoking [aOR 2.2; 95% confidence interval (CI) 1.1; 4.7], older age (aOR 1.6; 95% CI 1.2; 2.2), and lower CD4 count (aOR 0.8; 95% CI 0.7; 1.0). CONCLUSIONS: Airflow obstruction was relatively uncommon. Our findings suggest that PLWHIV who are ≥50 years old, smokers and those with nadir CD4 counts ≤ 200 cells/µL could be targeted to undergo spirometry to diagnose chronic airflow obstruction.

Hypertension and antihypertensive treatment in veterans with spinal cord injury and disorders.

OBJECTIVES: Hypertension (HTN) is an important risk factor for cardiovascular disease, a major cause of morbidity and mortality among people with spinal cord injury and disorders (SCI/D). Our study examined prevalence, associated factors, and pharmacological treatment of HTN in Veterans with SCI/D compared with a matched control group. METHODS: A retrospective review was conducted of Veterans with traumatic SCI/D (TSCI/D; n=6672), non-traumatic SCI/D (NTSCI/D; n=3566) and a matched, non-injured cohort. RESULTS: Over half of patients with TSCI/D (56.6%) had HTN, compared with 68.4% of matched controls (P<0.001). Paraplegic and tetraplegic Veterans with TSCI/D had significantly lower odds of having a HTN diagnosis compared with control (odds ratios (OR)=0.84 (0.77-0.91); OR=0.38 (0.35-0.42)). About 71.8% of patients with NTSCI/D had HTN compared with 72.3% of matched controls (P>0.05). Paraplegic and tetraplegic Veterans with NTSCI/D did not have significantly different odds of a HTN diagnosis compared with control (OR=0.92 (0.79-1.05); OR=0.85 (0.71-1.01)). Adjusted analysis indicates that Veterans with tetraplegia and HTN were less likely to receive antihypertensive therapy (TSCI/D, OR=0.62 (0.53-0.71); NTSCI/D, OR=0.81 (0.66-0.99)). CONCLUSION: HTN appears to be more prevalent in SCI/D Veterans than previously reported. TSCI/D Veterans have a significantly lower prevalence of HTN whereas NTSCI/D Veterans have a comparable prevalence of HTN to those without SCI/D. The level of injury (tetraplegia vs paraplegia) has a large impact on the prevalence of HTN in the traumatic cohort. Subsequent antihypertensive therapy is used less in both TSCI/D and NTSCI/D Veterans with tetraplegia and more in TSCI/D Veterans with paraplegia.

Selective Lesioning of Nuclear Factor-κB Activated Cells in the Nucleus Accumbens Shell Attenuates Alcohol Place Preference.

Nuclear factor κ-light chain enhancer of activated B cells (NF-κB) is a transcription factor commonly associated with innate immunity and is activated by infection and inflammation. NF-κB has recently gained attention as a mediator of complex psychiatric phenomena such as stress and addiction. In regards to alcohol, most research on NF-κB has focused on neurotoxicity and few studies have explored the role of NF-κB in alcohol reward, reinforcement, or consumption. In these studies, we used conditioned place preference to assess the activity of NF-κB in response to rewarding doses of alcohol. To measure NF-κB activity we used a line of transgenic mice that express the LacZ gene under the control of an NF-κB-regulated promoter. In these animals, staining for ß-galactosidase (ß-gal) identifies cells in which NF-κB has been activated. We then used the Daun02 inactivation method to specifically silence NF-κB-expressing cells during place preference conditioning. Daun02 is an inactive prodrug that is converted to the inhibitory molecule daunorubicin by ß-gal. After alcohol place conditioning, we observed increased ß-gal staining in the nucleus accumbens (NAC) shell and dorsal raphe nucleus, and found that disruption of NF-κB-expressing cells using Daun02 attenuated the development of alcohol place preference when infused into the NAC shell following conditioning sessions. We found this effect to be regionally and temporally specific. These results suggest that, in addition to its role in alcohol-induced neurotoxicity, NF-κB mediates the development of alcohol place preference via its actions in the NAC shell.

Calcium modulation of phorbol ester-induced alterations in murine macrophage morphology.

The phorbol ester tumor promoter phorbol-12-myristate-13-acetate (PMA) induced mouse resident peritoneal macrophage spreading in an in vitro system in a time- and dose-dependent manner; this process was modified by agents which alter intracellular calcium metabolism. After a 35-min incubation with PMA, 50% of the macrophages were spread (as classified by at least a 2-fold increase in cell surface area). Also at 35 min, the median effective concentration for PMA induction of spreading was 1.6 ng/ml. The intracellular calcium antagonist 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate inhibited PMA-induced cell spreading with a one-half maximal inhibitory concentration of 8.0 microM. The calcium ionophore A23187 enhanced PMA-induced spreading by 30% at 0.1 to 10 nM. The histological dye ruthenium red, which purportedly increases intracellular calcium by displacing membrane-bound calcium stores, enhanced PMA-induced spreading up to 75% at 1.0 pM. The cationic chelator ethyleneglycolbis(beta-aminoethylether)-N,N-tetraacetic acid (1.8 and 3.6 mM) had no effect on PMA-induced spreading. Thus, PMA-induced spreading was independent of extracellular calcium but was modulated by agents altering intracellular calcium metabolism. Microfilament formation, a proposed mechanism of cell spreading, also depends on intracellular calcium availability. The microfilament inhibitor cytochalasin B inhibited PMA-induced spreading with a one-half maximal inhibitory concentration of 1 microM. Future experiments should investigate the hypothesis that calcium availability to the cytoskeletal elements regulates the morphological effects of PMA on macrophages.

Extracellular calcium requirement for promotion of transformation in JB6 cells.

Extracellular calcium is required in the induction of neoplastic transformation of preneoplastic mouse JB6 epidermal cells by 12-O-tetradecanoylphorbol-13-acetate (TPA). Depleting extra-cellular calcium by chelation or by use of commercial calcium-depleted medium inhibited TPA-promoted transformation of promotion-sensitive JB6 cells with a half-maximal inhibition at 1.2 mM calcium. Inhibition was reversible by the addition of calcium. The calcium channel blockers lanthanum and nifedipine inhibited promotion of anchorage-independent transformation by TPA maximally at 10.0 microM and 1.0 nM, respectively, suggesting that calcium entry occurs partially via cell channels. None of the above treatments altered expression of transformation in anchorage-independent tumorigenic JB6 cell lines, indicating that the extracellular calcium requirement was at the level of induction, not expression of transformation. The calcium requirement was not merely a requirement for proliferation; calcium concentrations from 0.2 to 1.8 mM had no effect on JB6 cell monolayer growth. Extracellular calcium was required for 7 days for maximal colony induction. The calcium ionophore A23187 was not a promoter and moderately inhibited TPA-promoted transformation, indicating that increases in free cytosolic calcium concentrations are not sufficient for promotion of transformation and may even activate calcium-dependent antipromoting events. The results suggest that a cellular calcium pool supplied by extracellular calcium, but not distinguishable by ionophoretic increases in free cytosolic calcium, is essential in TPA-promoted neoplastic transformation.

Comparison of mouse pro-1 and pro-2 transfectants for responses to tumor promoters and antipromoters.

A previous report demonstrated that mouse JB6 cells transformed to promotion sensitive (P+) phenotype by transfection with an activated promotion sensitivity (pro) gene showed both evidence for the presence of the transfected gene and sensitivity to phorbol ester induced transformation similar to that observed in parental P+ cells. In addition, pro-1 and pro-2 transfectants were similar to each other in phorbol ester response. The current report extends these findings to ask whether pro-1 or pro-2 transfectants are also sensitive to promotion of transformation by other classes of tumor promoters such as epidermal growth factor (EGF), lanthanides, and phthalate esters and to inhibition of phorbol ester promoted transformation by several classes of antipromoters. The results showed that both pro-1 and pro-2 transfectants resembled parental P+ cells in sensitivity to promotion of anchorage independent transformation by lanthanides and by diethylhexylphthalate. In addition both pro-1 and pro-2 transfectants showed inhibition of phorbol ester induced transformation by antipromoters ganglioside GT1b, ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and forskolin. Thus the pathways implicated by these inducers and inhibitors of transformation appear similar to those implicated for parental P+ cells and similar when controlled by pro-1 or pro-2. The single differential response was that of EGF-induced transformation. pro-2 transfectants but not pro-1 transfectants were sensitive to EGF-induced neoplastic transformation. The nonresponsiveness could not be attributed to lack of EGF receptors since 125I-EGF binding to pro-1 transfectants was similar to that for pro-2 transfectants and parental P+ cells. Thus pro genes transfer responsiveness to a C-kinase mediated promotion of transformation pathway and to putatively non-C kinase pathways triggered by lanthanides or phthalate esters, but not necessarily to an EGF receptor kinase mediated pathway.

Transfer by pro gene transfection of tumor promoter-sensitive phenotype to promotion-insensitive JB6 cells.

Transfection of activated promotion sensitivity genes (pro genes) confers on insensitive (P-) cells susceptibility to induction of anchorage-independent growth by tumor-promoting phorbol esters. Promotion-sensitive (P+) JB6 cell variants, from which activated pro-1 and pro-2 were cloned, respond to 12-O-tetradecanoylphorbol-13-acetate (TPA) and various nonphorbol tumor promoters with anchorage-independent transformation that is irreversible 60-80% of the time. Anchorage-independent (Tx) clonal lines derived from these TPA-induced agar colonies were also tumorigenic in nude mice. This report has addressed the question of whether the phenotypes associated with parental P+ cells are transferred by transfection of activated pro-1 and pro-2. Clonal lines were established after transfection of JB6 P- cells with activated pro-1 or pro-2, induction of anchorage-independent colony formation by TPA, and growth of individual agar colonies to yield clonal transfectant lines. The lines so derived from transfected populations included Tx, P+, and P- lines, reflecting irreversible neoplastic transformation and greater and lesser degrees of preneoplastic progression, respectively. The anchorage-independent transfectants were found to be tumorigenic. Since untransfected P- cells subjected to the same single-cycle TPA treatment and cloning in agar yielded no anchorage-independent and few P+ transfectants, the appearance of P+ and Tx transfectants after pro-1 and pro-2 transfection is therefore likely to be due to the transfected pro genes. Indirect assay of pro gene uptake by quick-blot hybridization of transfectant cell DNA with the vectors into which pro genes had been cloned confirmed the association of transferred P+ and Tx phenotypes with the presence of the transfected DNA. Finally, assay of the sensitivity of P+ pro-1 and pro-2 transfectants to transformation by TPA at various concentrations showed that transfection with pro-1 or pro-2 conferred about equal responses that were somewhat lower than those observed with parental P+ controls. Taken together these data indicate that promotion-insensitive JB6 cells need only an activated pro gene and TPA exposure to become neoplastically transformed.

Antagonist of phorbol ester receptor-mediated chemotaxis in mouse peritoneal macrophages.

Biologically active phorbol ester derivatives displace [3H]phorbol-12, 13-dibutyrate from thioglycollate-elicited mouse peritoneal macrophages in a time-, temperature-, and concentration-dependent manner. Scatchard analysis revealed an apparent Kd of 54.1 nM and 8.0 X 10(5) sites/cell, indicating that these macrophages possess saturable, high-affinity phorbol ester-binding sites. These derivatives also act as chemoattractants for the macrophage at equivalent concentrations. A notable exception to this pattern is phorbol-12,13-diacetate. Phorbol-12,13-diacetate inhibits specific binding of [3H]phorbol-12,13-dibutyrate (concentration required for a 50% inhibition of the maximum specific binding of [3H]phorbol-12,13-dibutyrate, 2.6 microM) and chemotaxis to phorbol-12-myristate, 13-acetate (concentration required for a 50% inhibition of the maximum chemotactic response, 0.39 microM) while exhibiting no activity as a chemoattractant at concentrations up to 10(-5) M. The data indicate that phorbol-12,13-diacetate may be an antagonist for receptor-mediated chemotaxis to phorbol-12-myristate, 13-acetate in the macrophage.

Quantitative polymerase chain reaction for the detection of micrometastases in patients with breast cancer.

PURPOSE: Previous reports have indicated that reverse transcriptase polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK-19) may be useful in the management of patients with breast cancer. However, the specificity of this technique is low, principally because of a high rate of false-positive results. To improve the specificity of this assay, we developed a quantitative RT-PCR methodology that enables an estimate to be made of the number of CK-19 transcripts in blood and bone marrow samples. PATIENTS AND METHODS: We examined 45 peripheral-blood samples and 30 bone marrow samples from patients with a variety of nonneoplastic conditions using nested RT-PCR for CK-19. We also examined bone marrow and peripheral-blood samples from 23 patients with primary breast cancer and peripheral-blood samples from 37 patients with metastatic breast cancer. The number of CK-19 transcripts was estimated in positive specimens by competitive PCR and normalized to the number of ABL transcripts as an internal control for the quality and quantity of cDNA. RT-PCR results were compared with the numbers of CK-19-positive cells detected by immunocytochemistry. RESULTS: Analysis of samples from patients without cancer enabled us to define an upper limit for the background ratio of CK-19 to ABL transcripts (1:1,000 for blood samples and 1:1,600 for bone marrow samples). Using these figures as cut-off points, elevated CK-19: ABL ratios were detected in peripheral-blood samples of 20 of 37 (54%) patients with metastatic breast cancer and in bone marrow samples of 14 of 23 (61%) patients with primary breast cancer. Only three of 23 (13%) primary breast cancer peripheral-blood samples and none of the control samples were positive by these criteria. Only two of 23 patients (9%) with primary breast cancer showed immunocytochemically detectable cells in the blood; 10 of 23 (43%) showed immunocytochemically detectable cells in the bone marrow. Of 36 patients with metastatic breast cancer, eight (22%) showed positive events. CONCLUSION: Quantitative RT-PCR for CK-19 detects a percentage of patients with breast cancer and may enable the progression or regression of the disease to be monitored.

Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemical techniques.

PURPOSE: We previously developed a quantitative system for the detection of cytokeratin 19 (CK-19) transcripts using reverse transcriptase polymerase chain reaction (PCR) to detect breast carcinoma cells in blood and bone marrow. The aim of this study was to determine the value of this system in monitoring patients with metastatic disease and to compare it with an established immunocytochemical method. PATIENTS AND METHODS: Patients with progressive, locally advanced, and metastatic breast cancer (all stage IV) who were due to start systemic treatment were recruited. Blood samples were analyzed for CK-19 transcripts using quantitative PCR (QPCR) and immunocytochemistry (ICC) throughout their course of treatment. RESULTS: One hundred forty-five blood samples were obtained from 22 patients over 13 months. Seventy-two (49.6%) of these samples were positive by QPCR, and 56 (42%) of 133 were positive by ICC. Of the 133 specimens analyzed by both techniques, 95 (71.4%) had the same results for each, and of the 71 samples that were positive, 40 (56%) were positive by both methods. The relationship between the number of cells detected and the QPCR values was statistically significant (P <.0001). Of the 25 courses of assessable treatment, 17 (68%) of 25 treatment outcomes (either response or disease progression) were reflected by QPCR measurements, and 12 (57%) of 21 were reflected by ICC. During the course of the study, five patients showed a response, and of these, ICC was in agreement in four cases (80%) and QPCR in three cases (60%). Eighteen courses of treatment resulted in progression of the disease; however, only 15 of these were assessable by ICC. ICC was in agreement in eight (53%) of 15 of these cases, and QPCR in 15 (83%) of 18 cases. CONCLUSION: Circulating carcinoma cells are frequently found in patients with metastatic breast cancer. In the majority of patients, cancer cell numbers as evaluated by QPCR or ICC reflected the outcome of systemic treatment.

Microsatellite alterations plasma DNA of primary breast cancer patients.

The aim of this study was to analyze plasma DNA from primary and metastatic breast cancer cases for tumor-specific alterations and to compare these findings with immunocytochemistry and estimation of cytokeratin 19 (CK19) mRNA for detection of micrometastases. DNA was extracted from plasma, lymphocytes, and microdissected tumor tissue sections obtained from 71 patients with breast cancer and 9 controls. DNA samples were analyzed for loss of heterozygosity (LOH) and/or microsatellite instability (MI) by PCR with two polymorphic markers (DM-1 and D16S400). Reverse transcription-quantitative PCR (QPCR) and immunocytochemistry were used for detection of CK19 mRNA and protein. Breast cancer plasma DNA displayed frequent LOH (31.3%) and MI (11.6%) supported by the same alteration in microdissected tumor DNA. Most notably, 10 of the 39 patients with primary breast cancer showed LOH (n = 6) or MI (n = 4). We compared plasma tumor DNA, plasma and bone marrow QPCR, and blood and bone marrow immunocytochemistry in 32 of the patients with primary cancer. Of these, only one patient had immunocytochemically detectable carcinoma cells in the blood, and three showed abnormally high levels of plasma CK19 mRNA. All four of these patients had plasma DNA alterations. We then compared bone marrow findings: of the 10 primary breast cancers that showed LOH or MI, 6 had elevated CK19 mRNA and 5 had immunocytochemically positive cells. Tumor DNA is readily detectable in plasma of primary and metastatic breast cancer patients, and plasma DNA alterations (LOH and MI) reflect those seen in the tumor. The application of microsatellite analyses to plasma DNA may be useful in assessing tumor burden in breast cancer patients, particularly when combined with QPCR, and is preferable for patients with breast cancer, for whom sequential bone marrow aspiration is undesirable.

Implementing a declination form programme to improve influenza vaccine uptake by staff in Department of Veterans Affairs spinal cord injury centres: a pilot study.

BACKGROUND: Individuals with spinal cord injuries and disorders are at high risk for respiratory and influenza-related complications after developing influenza. These individuals often have frequent contact with the healthcare system. Vaccination rates in healthcare workers at Department of Veterans Affairs (VA) spinal cord injury (SCI) centres have been approximately 50% for several years. Efforts are needed to increase vaccination uptake among SCI HCWs. Declination form programmes (DFPs) in combination with other strategies have resulted in significant increases in influenza vaccination uptake in HCWs. AIM: Use of external and internal facilitation including local teams and consensus processes to pilot a DFP in two VA SCI centres and evaluate factors influencing implementation. METHODS: Implementation meetings and a consensus-building process with leadership and implementation team members were conducted, along with semi-structured post-implementation interviews with members of each implementation team (N = 7). FINDINGS: The DFP was well accepted and easy to use. Leadership was a key facilitator for DFP implementation. Barriers included difficulty communicating with HCWs working during early/late shifts. Participation was 100% at Site 1 and 48% at Site 2. CONCLUSION: Use of local teams and consensus to identify strategies to implement a DFP is feasible and effective for achieving moderate-to-high levels of participation in the programme.

Alterations in calcium metabolism in phorbol ester-treated mouse peritoneal macrophages.

Phorbol 12-myristate 13-acetate (PMA)-treated macrophages exhibited a two-fold increase in the rate of 45Ca++ efflux and over a three-fold increase in the size of the exchangeable calcium pool, resulting in almost a seven-fold increase in the slow phase of calcium efflux. The calcium antagonist 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) by itself did not affect calcium efflux in macrophages; but abolished the PMA-induced increase in the rate of calcium efflux. The divalent cationphore A23187 increased the rate constant of the fast phase of calcium efflux two-fold when applied alone or when applied with PMA. These effects might be linked to ionophore enhancement and TMB-8 inhibition of PMA-induced macrophage chemotaxis and spreading (previously reported in Cell Calcium 3:503-514 and Cancer Research 43:3385-3391). No change in calcium efflux was observed if cells were exposed to PMA only during the efflux experiment suggesting that a prolonged exposure to PMA is required to elicit changes in calcium flux. Increased 45Ca++ remained in treated cells at each time point perhaps reflecting the PMA-induced increase in exchangeable calcium.

The role of calcium in macrophage chemotaxis to the phorbol ester tumor promoter TPA.

The significance of the macrophage in the inflammatory response that occurs concurrently with phorbol ester induced tumor promotion has not yet been determined. Biologically active phorbol ester tumor promoters modify several functional responses of macrophages including chemotaxis, cytotoxicity, secretion and prostaglandin synthesis and release. The present study examines calcium metabolism as a possible underlying biochemical mechanism through which 12-0-tetradecanoyl-phorbol-13-acetate (TPA) exerts its effects on macrophage chemotaxis. The chemotaxis of mouse resident peritoneal macrophages was evaluated in the presence of pharmacological agents known to alter cellular calcium metabolism. The calcium ionophore A23187 in microM concentrations enhanced macrophage chemotaxis to TPA by approximately 41%. This enhancement was dependent on the presence of extracellular calcium. TPA-induced chemotaxis was also enhanced by the histological dye ruthenium red (RR), an agent known to modify mitochondrial calcium fluxes and calcium-dependent neuronal transmission. Ruthenium red (0.1 and 1.0 microM) produced a maximal stimulation of macrophage chemotaxis to TPA of approximately 62%. An intracellular calcium antagonist, 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) inhibited macrophage chemotaxis to TPA in a dose related fashion (1.0 to 100 microM). Varying extracellular calcium concentrations (0-3.6 mM) had no effect on macrophage chemotaxis in response to TPA. In drug combination studies neither A23187 nor RR was able to overcome the inhibitory effects of TMB-8 on macrophage chemotaxis to TPA. These results indicate that intracellular calcium metabolism may be playing a significant role in modulating TPA's effect on macrophage chemotaxis, while extracellular calcium may be of little import. A possible mode of TPA's effect on the macrophage via mobilization of calcium from cellular storage sites is discussed.

Unaltered lymphocyte beta-adrenoceptor responsiveness in hyperthyroidism and hypothyroidism.

Beta adrenoceptor sensitivity may be altered in thyrotoxicosis and myxedema. We therefore studied beta-adrenoceptor responses of peripheral blood lymphocytes to stimulation with 10(-9) to 10(-6) M (-)-isoproterenol from patients before and after treatment of myxedema and thyrotoxicosis as well as in patients without thyroid disease. There were six patients in each group. Lymphocyte basal cyclic adenosine monophosphate (cAMP) concentrations were higher in untreated thyrotoxicosis (4.94 +/- 0.46 pmole/10(6) cells) than in controls (3.47 +/- 0.42 pmole/10(6) cells, p less than 0.05) and in untreated myxedema (3.11 +/- 0.50 pmole/10(6) cells, p less than 0.025). The full isoproterenol dose-response curves were similar in all groups. Calculated maximum velocity (Vmax) showed an approximate increase in cAMP of 14.5 pmole/10(6) cells. Isoproterenol concentrations at half-maximum velocity (EC50) were approximately 10(-8) M. It is concluded that lymphocyte beta 2-adrenoceptor responses are not altered in hypothyroidism and hyperthyroidism.

Cardiovascular and renal benefits of dry bean and soybean intake.

Dry beans and soybeans are nutrient-dense, fiber-rich, and are high-quality sources of protein. Protective and therapeutic effects of both dry bean and soybean intake have been documented. Studies show that dry bean intake has the potential to decrease serum cholesterol concentrations, improve many aspects of the diabetic state, and provide metabolic benefits that aid in weight control. Soybeans are a unique source of the isoflavones genistein and diadzein, which have numerous biological functions. Soybeans and soyfoods potentially have multifaceted health-promoting effects, including cholesterol reduction, improved vascular health, preserved bone mineral density, and reduction of menopausal symptoms. Soy appears to have salutary effects on renal function, although these effects are not well understood. Whereas populations consuming high intakes of soy have lower prevalences of certain cancers, definitive experimental data are insufficient to clarify a protective role of soy. The availability of legume products and resources is increasing, incorporating dry beans and soyfoods into the diet can be practical and enjoyable. With the shift toward a more plant-based diet, dry beans and soy will be potent tools in the treatment and prevention of chronic disease.

Effects of soy protein on renal function and proteinuria in patients with type 2 diabetes.

For > 150 y, clinicians and investigators have observed that high protein intakes accelerate the progression of renal disease and that low protein intakes have beneficial effects. Some studies suggest that the effects of soy-protein intake resemble those of a low-protein diet. The Brenner hypothesis suggests that high protein intakes by diabetic individuals create hyperfiltration and glomerular hypertension eventuating in renal damage. On the basis of the available evidence, we are proposing the soy-protein hypothesis, which states that substituting soy protein for animal protein in diabetes patients results in less hyperfiltration and glomerular hypertension and, therefore, resultant protection from diabetic nephropathy. Furthermore, substituting soy protein for animal protein should have therapeutic value in diabetic nephropathy with resultant slowing of deterioration of renal function and decreasing proteinuria. The preliminary results of the study of 8 type 2 diabetes patients with obesity, hypertension, and proteinuria are reported. Under the conditions of the study, providing soy protein as half of the daily protein intake had no distinct effects on renal function or proteinuria in these subjects. Soy-protein intake was associated with a significant reduction in serum cholesterol and triacylglycerol concentrations. Further studies are required to critically examine the effects of soy-protein intake on the renal function of diabetes patients.

Health benefits and practical aspects of high-fiber diets.

Over the past 20 y dietary fiber has emerged as a leading dietary factor in the prevention and treatment of chronic diseases. High fiber intakes are associated with lower serum cholesterol concentrations, lower risk of coronary heart disease, reduced blood pressure, enhanced weight control, better glycemic control, reduced risk of certain forms of cancer, and improved gastrointestinal function. Dietary fiber can be categorized into water-soluble and water-insoluble components. Dried beans, oat products, and certain fruits and vegetables are good sources of soluble fiber. Most plant foods are good sources of insoluble fiber and wheat bran is a concentrated form of insoluble fiber. Current guidelines advise a doubling of dietary fiber intake for Americans. Inclusion of ample servings of fruits and vegetables, whole grains, and dried beans and peas will help individuals meet these guidelines.

Prospective, randomized, controlled comparison of the effects of low-fat and low-fat plus high-fiber diets on serum lipid concentrations.

Previous studies examining the hypocholesterolemic effects of high-soluble-fiber diets have not been designed to control for dietary fat intake. Serum cholesterol reductions may therefore be accounted for by differences in consumption of fat. Moderately hypercholesterolemic, nonobese, Caucasian men and women, 30-50 y old were randomly assigned to low-fat, low-fat plus high-fiber, or usual-diet groups and followed for 12 mo. At 12 mo the high-fiber group consumed significantly more soluble fiber than both the low-fat and usual-diet groups (P = 0.0063 and P = 0.0001); the high-fiber group did not differ from the low-fat group in quantity of dietary fat consumed. The high-fiber group experienced a greater average reduction (13%) in serum cholesterol than did the low-fat (9%) and usual-diet (7%) groups. After adjustment for relevant covariates, the reduction in the high-fiber group was significantly greater than that in the low-fat group (P = 0.0482). Supplementation with soluble fiber reduces serum cholesterol beyond the reduction observed with low-fat diet alone.

Renovascular hypertension: anatomic and renal function changes during drug therapy.

Serial renal function studies were performed on 41 patients wtih renovascular hypertension (RVH) secondary to atherosclerotic renal artery disease who had been randomly selected for nonoperative management. In 19 patients, serum creatinine levels increased between 25% and 120%. The glomerular filtration rates dropped between 25% and 50% in 12 patients. Fourteen patients (37%) lost more than 10% of renal length. In four patients (12%), a significant stenosis progressed to total occlusion. Seventeen patients (41%) had deterioration of renal function or loss of renal size that led to operation. One patient required removal of a previously reconstructible kidney. Of the 17 patients with deterioration, 15 had acceptable blood pressure (BP) control during the period of nonoperative observation. Progressive deterioration of renal function in nonoperatively treated patients with atherosclerotic renal artery stenosis and RVH is common, and occurs even in the presence of BP control with drugs.