Microbial biofilms in nature: unlocking their potential for agricultural applications.

Soil environments are dynamic and the plant rhizosphere harbours a phenomenal diversity of micro-organisms which exchange signals and beneficial nutrients. Bipartite beneficial or symbiotic interactions with host roots, such as mycorrhizae and various bacteria, are relatively well characterized. In addition, a tripartite interaction also exists between plant roots, arbuscular mycorrhizal fungi (AMF) and associated bacteria. Bacterial biofilms exist as a sheet of bacterial cells in association with AMF structures, embedded within a self-produced exopolysaccharide matrix. Such biofilms may play important functional roles within these tripartite interactions. However, the details about such interactions in the rhizosphere and their relevant functional relationships have not been elucidated. This review explores the current understanding of naturally occurring microbial biofilms, and their interaction with biotic surfaces, especially AMF. The possible roles played by bacterial biofilms and the potential for their application for a more productive and sustainable agriculture is discussed in this review.

FUNGAL SYMBIONTS. Global assessment of arbuscular mycorrhizal fungus diversity reveals very low endemism.

The global biogeography of microorganisms remains largely unknown, in contrast to the well-studied diversity patterns of macroorganisms. We used arbuscular mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to determine the global distribution of these plant symbionts. We found that AM fungal communities reflected local environmental conditions and the spatial distance between sites. However, despite AM fungi apparently possessing limited dispersal ability, we found 93% of taxa on multiple continents and 34% on all six continents surveyed. This contrasts with the high spatial turnover of other fungal taxa and with the endemism displayed by plants at the global scale. We suggest that the biogeography of AM fungi is driven by unexpectedly efficient dispersal, probably via both abiotic and biotic vectors, including humans.

The need to lower systolic blood pressure.

Systolic hypertension is the most common form of hypertension, especially in individuals aged 60 years or older. Systolic hypertension is a reflection of decreasing compliance of large arteries and is a strong independent risk factor for all cardiovascular diseases. Despite proven benefits of therapy for systolic hypertension, only 25% of patients with this condition are adequately treated to attain target blood pressures. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure (JNC VI) recommends the use of diuretics and long-acting dihydropyridine calcium channel blockers as first-line therapy for isolated systolic hypertension. Therapy is also guided by comorbid conditions where certain drugs may have additional benefits. The goal of therapy should be a graded reduction in blood pressure to less than 140/90 mm Hg with lower blood pressure targets in patients with coexistent diabetes or renal failure.

Management of postural hypotension.

Several mechanisms counteract the gravitational forces on blood and maintain systemic arterial pressure and cerebral perfusion upon assumption of the upright posture. Failure of these mechanisms can lead to a postural decrease in blood pressure. Postural hypotension is defined as a reduction of at least 20 mm Hg in systolic blood pressure or at least a 10 mm Hg decrease in diastolic blood pressure. Acute postural hypotension is usually due to fluid or blood loss and responds well to fluid repletion. Chronic postural hypotension is due to drugs or endocrine or neurogenic disorders. A functional classification based on severity of symptoms is useful in monitoring the patient's condition and documenting improvement with treatment. Whenever possible, the reversible causes of chronic postural hypotension should be treated. For symptomatic treatment, a stepped approach starting with nonpharmacologic measures is recommended. Fludrocortisone, midodrine, indomethacin, and atrial tachypacing are recommended, in that order, for patients in whom nonpharmacologic measures prove insufficient. Other drugs can be added if necessary. The goal of treatment is to make the patient as ambulatory and symptom-free as possible without causing supine hypertension.

Hypertension in women.

More women than men eventually develop hypertension in the United States due to their higher numbers and longer longevity. The white coat hypertension is also more common in women. Alcohol, obesity and oral contraceptives are important causes of rise in blood pressure among women. On the other hand, hormone replacement therapy may decrease cardiovascular mortality in the postmenopausal woman. Women with left ventricular hypertrophy are at a greater risk of death than men. Fibromuscular hyperplasia and primary aldosteronism are more common as causes of secondary hypertension in women. Nonpharmacologic therapy, such as weight reduction, exercise, salt and alcohol reduction, should always be tried prior to medical treatment of hypertension and are very useful adjunctive measures in controlling hypertension. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy and should be avoided in women with childbearing potential. Hypertension remains a major public health problem among black women. Although the antihypertensive drug therapy seems to benefit white women the least, proportionately more of them comply with their antihypertensive therapy. Hypertension is the most common chronic medical condition requiring visits to the physicians, as well as prescription medications, in the United States. The epidemiology, clinical course, response to treatment and ultimate outcome of essential hypertension may vary with gender. More women than men eventually develop hypertension in the US due to their higher numbers and longer longevity.

Effect of pain and nonsteroidal analgesics on blood pressure.

Acute pain increases blood pressure by increasing sympathetic activity, but the role of chronic pain on blood pressure is less well understood. Hypertension and co-existing musculoskeletal problems are two of the common conditions for which antihypertensives and analgesics are prescribed together. Among analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) are most frequently prescribed. NSAIDs decrease the synthesis of prostaglandins (PG) by inhibiting cyclo-oxygenase, an enzyme essential for transformation of arachidonic acid into PGs. The PGs are important in control of blood pressure by virtue of their effects on the kidney and blood vessels. Among the NSAIDs, indomethacin, naproxen and piroxicam have the greatest, and sulindac the least, pressor effect. The NSAIDs antagonize the antihypertensive effect of diuretics, beta-blockers and ACE inhibitors more than that of calcium-channel blockers. The elderly and those with salt-sensitive hypertension experience greater rise in blood pressure with NSAIDs. Physicians should avoid NSAIDs and instead use alternative analgesics such as acetaminophen and physical therapy for control of pain. If necessary, the dose of the antihypertensive medications may have to be increased for better control of blood pressure. It is commonly believed that acute pain increases blood pressure. The effect of chronic pain is less well understood. Certain analgesics may affect blood pressure and may interfere with the effects of antihypertensive therapy. Since both pain and hypertension are common, it is important that their relationship be well understood by the primary care physicians.

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension.

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from -3.5 for placebo, -7.1 to -10.2 for the irbesartan monotherapy groups, -5.1 to -8.3 for the HCTZ monotherapy groups, and -8.1 to -15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.

What is causing your patient's sexual dysfunction? Uncovering a connection with hypertension and antihypertensive therapy.

Arterial hypertension is associated with structural and functional alterations of the vessel walls. Because vascular endothelium plays a central role in the control of vascular tone, endothelial dysfunction can also cause certain types of erectile dysfunction. Erectile dysfunction is also a common side effect of certain drugs, including many antihypertensive agents. Physicians should be aware of potential sexual side effects of such drugs and take appropriate steps to alleviate persistent problems. Most important, physicians need to ask patients about sexual function and discuss the possibility of erectile dysfunction caused by antihypertensive therapy. Erectile dysfunction can be effectively treated in most patients, and many treatment options are available. Sildenafil therapy has revolutionized the management of this disorder, but this agent should be used with caution in certain patients taking nitrates.

Hyperhomocysteinemia: an additional cardiovascular risk factor.

Over the past few years, a substantial body of evidence has accumulated that indicates hyperhomocysteinemia as a significant risk factor for cardiovascular disease. Hyperhomocysteinemia arises from a lack of key enzymes or vitamins such as methylenetetrahydrofolate reductase, vitamin B6, and folate which are involved in homocysteine metabolism. Heavy coffee consumption is also known to elevate homocysteine levels. The adverse effects associated with hyperhomocysteinemia are extensive. It increases risk of myocardial infarction, cardiovascular-related morbidity and mortality, peripheral vascular disease, atherosclerosis, coronary heart disease, and cerebrovascular disease. Its seriousness as a risk factor has been equated to hypercholesterolemia and smoking, two leading causes for cardiovascular disease. It also has been shown to produce a multiplicative effect with these and other risk factors such as hypertension. Two major hypotheses have been proposed to explain how homocysteine induces its harmful effects. It can damage endothelial cells lining the vasculature, allowing plaque formation. Simultaneously, it interferes with the vasodilatory effect of endothelial derived nitric oxide. Also, homocysteine has been found to promote vascular smooth muscle cells hypertrophy. Both of these processes induce vessel occlusion. Maintaining a normal plasma level of homocysteine as a means to prevent cardiovascular disease appears promising. This is achieved through increased intake of folate and vitamin B6 through diet or supplementation. Despite the overwhelming evidence suggesting homocysteine as a significant risk factor, no long-term prospective studies have been completed to demonstrate that folate and vitamin B6 can prevent cardiovascular disease related morbidity and mortality in patients with hyperhomocysteinemia. Homocysteine is a key metabolite in amino acid synthesis. During the process of methylation, S-adenosylmethionine (Ado Met), derived from methionine, is converted to S-Adenosylhomocysteine (Figure 1). This product is quickly hydrolyzed to form homocysteine and adenosine. Homocysteine can undergo 1 of 3 reactions depending on the status of the organism. If cysteine levels are inadequate, homocysteine utilizes the coenzyme pyridoxal phosphate (vitamin B6) to condense with serine, forming the intermediate cystathionine. Subsequent reactions with cystathionine lead to the formation of cysteine. When methionine levels are low, homocysteine is remethylated in a reaction involving the coenzyme N5-methyltetrahydrofolate or betaine. Finally, when both amino acids are in adequate supply, homocysteine is cleaved by the enzyme homocysteine desulthydrase (cystathionase) to form a-ketobutyrate, ammonia, and H2S. Thus, homocysteine's physiological role is to assist in maintaining sulfur-amino acid homeostasis. Beyond these metabolic processes, homocysteine is beginning to be recognized as a significant risk factor for cardiovascular disease including atherosclerosis, coronary artery disease, cerebrovascular disease, and myocardial infarction.

The costs versus the perceived benefits of an LCME institutional self-study.

PURPOSE: To calculate the costs versus the perceived benefits of an institutional self-study done to satisfy the requirements of the Liaison Committee on Medical Education's (LCME's) accreditation process. METHOD: From postcard questionnaires, the authors determined the hours spent over 18 months from 1994 to 1996 on the institutional self-study by 131 self-study committee members and 64 database compilers at the Medical College of Wisconsin. The committee members also rated the potential utility of the self-study process and the probability that the concerns identified by their subcommittees would be addressed. Administrative costs (self-study coordinating team's hours, supplies, and other expenses) were tracked using calendars and budget subaccount numbers. Personnel costs were calculated using salary data from the Association of American Medical Colleges and the College and Universities Personnel Administrators' survey. RESULTS: Supplies and equipment for the self-study cost $12,158, and the personnel costs, based on an 81% response rate, were estimated at $207,384, for a total of $219,542. The participants in the self-study rated the process as moderately useful, but believed that there was only a medium degree of probability that concerns they had identified would be addressed. CONCLUSION: Considering the costs of self-study, the process might be more useful if attention were focused less on identifying concerns and more on an institution's demonstrated ability to successfully respond to problems.

Stress and hypertension.

Stress can cause hypertension through repeated blood pressure elevations as well as by stimulation of the nervous system to produce large amounts of vasoconstricting hormones that increase blood pressure. Factors affecting blood pressure through stress include white coat hypertension, job strain, race, social environment, and emotional distress. Furthermore, when one risk factor is coupled with other stress producing factors, the effect on blood pressure is multiplied. Overall, studies show that stress does not directly cause hypertension, but can have an effect on its development. A variety of non-pharmacologic treatments to manage stress have been found effective in reducing blood pressure and development of hypertension, examples of which are meditation, acupressure, biofeedback and music therapy. Recent results from the National Health and Nutrition Examination Survey indicate that 50 million American adults have hypertension (defined to be a systolic blood pressure of greater than 139 mm Hg or a diastolic blood pressure of greater than 89 mm Hg). In 95% of these cases, the cause of hypertension is unknown and they are categorized as "essential" hypertension. Although a single cause may not be identified, the general consensus is that various factors contribute to blood pressure elevation in essential hypertension. In these days of 70 hour work weeks, pagers, fax machines, and endless committee meetings, stress has become a prevalent part of people's lives; therefore the effect of stress on blood pressure is of increasing relevance and importance. Although stress may not directly cause hypertension, it can lead to repeated blood pressure elevations, which eventually may lead to hypertension. In this article we explore how stress can cause hypertension and what can be done about it.

Calcium channel blockers. Consensus amid controversy.

Although the calcium channel blockers have been used to treat hypertension for a number of years, they are now under close scrutiny because of disturbing findings regarding their safety. Drs Kochar and Qurashi sort out the controversies surrounding these widely used drugs and make recommendations based on current consensus.

Detection of hepatitis B surface antigen in whole blood by coupled particle light scattering (Copalis).

Coupled particle light scattering (Copalis) is a homogeneous immunoassay technology that permits simultaneous determination of multiple analytes in serum, plasma, or whole blood. Copalis differentiates monomeric latex microparticles from latex aggregates and cells on the basis of their unique light scatter properties. Copalis readily discriminates small (approximately 0.1 micron) differences in latex microparticle size. Therefore, multiple simultaneous assays are configured by the use of mixtures of different-size latex microparticles. The Copalis research immunoassay for hepatitis B surface antigen (HBsAg) is configured in a sandwich format where the extent of light scatter histogram broadening due to HBsAg-mediated binding of colloidal gold to latex provides the basis for antigen quantification. Simultaneous Copalis forward- and wide-angle light scatter measurements allow discrimination of latex microparticles from the cell components of whole blood. Consequently, direct detection of HBsAg in unprocessed whole-blood samples by Copalis is feasible.

Comparison of plasma lipid and lipoprotein profiles in hypertensive black versus white men. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

An abnormal plasma lipid and lipoprotein profile is an independent and strong predictor of mortality and morbidity from coronary artery disease (CAD). We report on plasma lipid and lipoprotein profiles with respect to race, age, obesity, blood pressure (BP), smoking, and drinking history in 1,292 male veterans with a diastolic BP of 95 to 109 mm Hg while off antihypertensive medications. Blacks had 24% (p <0.001) lower triglycerides than whites. In contrast, the following parameters were higher in blacks than in whites by the indicated percentages: high-density lipoprotein (HDL) cholesterol, 16% (p <0.001); HDL2 cholesterol, 36% (p <0.001); apolipoprotein (Apo) A1, 8% (p <0.001); HDL/low-density lipoprotein (LDL), 18% (p = 0.018); HDL2/LDL, 36% (p = 0.031); HDL2/HDL3, 21% (p <0.001); and Apo A1/Apo B, 15% (p <0.001). Triglycerides were unchanged up to age 60, but were lower by 24% (p <0.001) in those aged > or = 70. Apo A1 levels were higher (p <0.001), whereas LDL cholesterol was lower (p <0.008) in moderate alcohol consumers versus abstainers. Triglycerides were higher (p <0.001), whereas HDL, HDL2 cholesterol, and Apo A1 were lower (p <0.001) with increasing obesity. Moderate alcohol consumption had a strong favorable effect on HDL, HDL2, and HDL3 cholesterol among subjects of normal weight, but this effect was diminished in obese subjects. Total and LDL cholesterol were higher by 6.4% (p = 0.001) and 9.4% (p <0.003), respectively, whereas HDL cholesterol remained unchanged in those with diastolic BP of 105 to 109 mm Hg versus those with diastolic BP of 95 to 99 mm Hg. We conclude that hypertensive black men have lipid and lipoprotein profiles indicative of less CAD risk than white men. Chronic moderate alcohol consumption correlates with a favorable plasma lipid and lipoprotein profile in normal, but not obese, men. Obesity is associated with an adverse plasma lipid and lipoprotein profile. Thus, race, alcohol intake, and obesity may be important modifiers of CAD in untreated hypertensive men.

The additive effects of smoking and hypertension. More reasons to help your patients kick the habit.

Although the link between cigarette smoking and its cardiovascular effects is well established, the mechanisms through which smoking raises blood pressure remain to be clarified. Possible mechanisms include nicotine-induced peripheral and central sympathetic nervous system stimulation, persisting levels of nicotine in blood because of incomplete metabolism, release of vasopressin, and chemoreceptor stimulation. Effects of nicotine on hemostasis, arterial rigidity, and vessel wall damage, together with detrimental effects on lipid metabolism, may contribute to an overall increased cardiovascular risk in smokers. Nonselective beta blockers are not as effective in smokers as they are in nonsmokers. Smoking cessation is a very important intervention in reducing cardiovascular risk in hypertensive patients. Physicians should counsel patients about smoking cessation at every visit. Use of the various smoking deterrents can help some patients quit.

A medical school-based GME consortium in Milwaukee.

Consortia have been recommended as a local mechanism for allocating housestaff positions and overseeing graduate medical education (GME) training programs. They also could serve to simplify the execution of a national health care policy in the future. Such a consortium has existed in Milwaukee for the last 16 years. It involves 23 health care institutions affiliated with the Medical College of Wisconsin. Known as the Medical College of Wisconsin Affiliated Hospitals, Inc. (MCWAH), this consortium employs 749 housestaff, for whom it provides salary and benefits. It also ensures accreditation of all of its residency and fellowship programs and assists in providing direction and coordination for the member institutions. The authors describe the genesis and operation of the MCWAH in detail. The accomplishments of existing consortia, in Milwaukee and elsewhere, indicate that a GME consortium should enable its members to function effectively and efficiently in meeting the challenging GME training requirements of the future.

Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected. OBJECTIVE: To analyze the antihypertensive response of patients who had failed to achieve their diastolic blood pressure goal (< 90 mm Hg at the end of 8 to 12 weeks of titration) with one of six randomly allocated drugs or placebo to the random allocation of an alternate drug. METHODS: We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug. RESULTS: Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies. CONCLUSIONS: We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.