Schistosoma mansoni co-infection modulates Chagas disease development but does not impair the effect of benznidazole-based chemotherapy.

The adequate management of parasite co-infections represents a challenge that has not yet been overcome, especially considering that the pathological outcomes and responses to treatment are poorly understood. Thus, this study aimed to evaluate the impact of Schistosoma mansoni infection on the efficacy of benznidazole (BZN)-based chemotherapy in Trypanosoma cruzi co-infected mice. BALB/c mice were maintained uninfected or co-infected with S. mansoni and T. cruzi, and were untreated or treated with BZN. Body weight, mortality, parasitemia, cardiac parasitism, circulating cytokines (Th1/Th2/Th17); as well as heart, liver and intestine microstructure were analyzed. The parasitemia peak was five times higher and myocarditis was more severe in co-infected than T. cruzi-infected mice. After reaching peak, parasitemia was effectively controlled in co-infected animals. BZN successfully controlled parasitemia in both co-infected and T. cruzi-infected mice and improved body mass, cardiac parasitism, myocarditis and survival in co-infected mice. Co-infection dampened the typical cytokine response to either parasite, and BZN reduced anti-inflammatory cytokines in co-infected mice. Despite BZN normalizing splenomegaly and liver cellular infiltration, it exacerbated hepatomegaly in co-infected mice. Co-infection or BZN exerted no effect on hepatic granulomas, but increased pulmonary and intestinal granulomas. Marked granulomatous inflammation was identified in the small intestine of all schistosomiasis groups. Taken together, our findings indicate that BZN retains its therapeutic efficacy against T. cruzi infection even in the presence of S. mansoni co-infection, but with organ-specific repercussions, especially in the liver.

Macroinvertebrates at the source: flow duration and seasonality drive biodiversity and trait composition in rheocrene springs of the Western Allegheny Plateau, USA.

Documenting flow regimes and the ecology of source headwater streams has gained considerable attention for scientific and regulatory purposes. These streams do not appear on standard maps, and local physiographic and climatologic conditions can control their origins. We investigated macroinvertebrate assemblages seasonally and in relation to flow duration, catchment and habitat variables within 14 source headwaters (< 1 ha) in the Western Allegheny Plateau over a 19-month period. We classified 6 perennial (P) and 8 intermittent (I) streams directly with continuous flow data loggers. Several biological and trait-based metrics could distinguish flow class, but few instream physical measures could. Macroinvertebrate metrics and assemblage dispersion varied seasonally and responded significantly along a gradient of total flow duration. Separate indicator species analyses generated 22 genera and 15 families with significant affinities to P streams. Richness of P-indicator taxa was also strongly correlated with flow duration gradients, and we estimated a total flow duration changepoint at 77% (3 indicator families) followed by a sharp increase in richness. Two rapid field-based flow duration methods (NC Stream Identification index and OH Headwater Habitat Evaluation index) could distinguish upstream ephemeral reaches from P and I reaches, but misclassified P as I more frequently. Our findings highlight that diverse coldwater macroinvertebrate assemblages inhabited extremely small, low-discharge springs in the region, and responded with flow duration. These source headwater habitats are susceptible to human disturbance and should be monitored as is routinely done in larger lotic systems.

Long-term impacts on macroinvertebrates downstream of reclaimed mountaintop mining valley fills in Central Appalachia.

Recent studies have documented adverse effects to biological communities downstream of mountaintop coal mining and valley fills (VF), but few data exist on the longevity of these impacts. We sampled 15 headwater streams with VFs reclaimed 11-33 years prior to 2011 and sampled seven local reference sites that had no VFs. We collected chemical, habitat, and benthic macroinvertebrate data in April 2011; additional chemical samples were collected in September 2011. To assess ecological condition, we compared VF and reference abiotic and biotic data using: (1) ordination to detect multivariate differences, (2) benthic indices (a multimetric index and an observed/expected predictive model) calibrated to state reference conditions to detect impairment, and (3) correlation and regression analysis to detect relationships between biotic and abiotic data. Although VF sites had good instream habitat, nearly 90 % of these streams exhibited biological impairment. VF sites with higher index scores were co-located near unaffected tributaries; we suggest that these tributaries were sources of sensitive taxa as drifting colonists. There were clear losses of expected taxa across most VF sites and two functional feeding groups (% scrapers and %shredders) were significantly altered. Percent VF and forested area were related to biological quality but varied more than individual ions and specific conductance. Within the subset of VF sites, other descriptors (e.g., VF age, site distance from VF, the presence of impoundments, % forest) had no detectable relationships with biological condition. Although these VFs were constructed pursuant to permits and regulatory programs that have as their stated goals that (1) mined land be reclaimed and restored to its original use or a use of higher value, and (2) mining does not cause or contribute to violations of water quality standards, we found sustained ecological damage in headwaters streams draining VFs long after reclamation was completed.

Survey of medication documentation at hospital discharge: implications for patient safety and continuity of care.

BACKGROUND: Medication discrepancies at the time of hospital discharge are common and can result in error, patient/carer inconvenience or patient harm. Providing accurate medication information to the next care provider is necessary to prevent adverse events. AIMS: To investigate the quality and consistency of medication details generated for such transfer from an Irish teaching hospital. METHODS: This was an observational study of 139 cardiology patients admitted over a 3 month period during which a pharmacist prospectively recorded details of medication inconsistencies. RESULTS: A discrepancy in medication documentation at discharge occurred in 10.8% of medication orders, affecting 65.5% of patients. While patient harm was assessed, it was only felt necessary to contact three (2%) patients. The most common inconsistency was drug omission (20.9%). CONCLUSIONS: Inaccuracy of medication information at hospital discharge is common and compromises quality of care.

Actions of R- and S-verapamil and nifedipine on rat vascular and intestinal smooth muscle.

1 We have investigated the actions of the calcium entry blockers nifedipine, R-verapamil and S-verapamil in rat aorta, colon and vas deferens. 2 In aorta and colon, these agents produced concentration-dependent relaxations of KCl (80 mM)-induced contractions. In both tissues, the order of potency was nifedipine > S-verapamil > R-verapamil. However, nifedipine showed selectivity for aorta (potency ratio, colon/aorta: 4.36), S-verapamil showed no selectivity (0.62), but R-verapamil showed selectivity for colon (0.19). 3 In prostatic portions of rat vas deferens, nifedipine (10 microM) abolished the contraction to a single electrical stimulus, but R- and S-verapamil were without effect. In epididymal portions of rat vas deferens, R- and S-verapamil inhibited alpha1-adrenoceptor-mediated contractions to a single electrical stimulus at concentrations of 10 microM and above. 4 In conclusion, R-verapamil may prove useful as an intestinal selective calcium entry blocker in the treatment of intestinal disease with a hypermotility component, e.g. irritable bowel syndrome.

Changing technology in health: product liability.

Greater health consumer awareness and increasing levels of concern for the rights of patients have led to patient care technology being more strictly regulated. This article analyses both the general law issues and the particular statutes that will be of relevance to those involved in evaluating and implementing such technologies. There are three main elements to this analysis. Firstly, there is the issue of liability for a product fault, which will in many cases be directed by legislation back to the manufacturer of the goods. Secondly, those involved in placement of patient care technology should be aware of anti-discrimination legislation when making placement decisions. Finally, occupational health and safety legislation sets minimum standards for technology used in healthcare facilities. The author suggests ways of complying with the laws for each regulatory regime.

Exercise groups in an insight-oriented, evening treatment program.

Exercise groups form an integral part of an insight-oriented, psychodynamic evening treatment program for a patient population characterized predominantly by mood and personality disorders. Clinical examples illustrate how the exercise groups are integrated with other therapy groups in the program. Therapists, who lead and participate in the exercise groups, attempt to maintain professional boundaries while they facilitate permissive activities where enactment of patient conflicts can occur. Events from the exercise groups frequently provide material for work in the more traditional psychodynamic groups of the program. A number of benefits of exercise groups are highlighted.

High-performance liquid chromatographic assay for diltiazem in small-volume blood specimens and application to pharmacokinetic studies in rats.

A high-performance liquid chromatographic (HPLC) method was developed which involves the use of two 5-microns BDS silica gel columns (15 cm x 4.6 mm I.D.) in series for increased resolution and sensitivity, and an organic mobile phase for both extraction and elution of diltiazem. Plasma samples (400 microliters) were extracted using the organic mobile phase [n-hexane-methanol-dichloromethane-ammonia (370:35:30:0.3)] and the extracts were monitored at 240 nm. Desipramine (30 micrograms ml-1) was the internal standard. The limit of quantification in plasma was 20 ng ml-1 with a correlation coefficient of > or = 0.999 within the 20-800 ng ml-1 standard window. The inter- and intra-assay R.S.D.s were within 5%. The recovery of diltiazem varied from 101.1% at 20 ng ml-1 to 93.7% at 400 ng ml-1. The method was applied to the investigation of diltiazem absorption in a rat. Drug absorption was based on the intestinal single-pass perfusion model. The concentration of diltiazem in all test perfusion solutions was 1 mg ml-1 (2.4 mM) and the flow-rate through the system was 3.33.10(-3) ml s-1. A non-specific mucolytic absorption enhancer was also added to a diltiazem solution and studied in the in situ system. The pharmacokinetics of diltiazem hydrochloride were investigated in two study groups of Wistar rats (n = 4). A two-sample Student's t-test was employed to compare values of the area under the curve (AUC). The pharmacokinetic data indicated that the AUC in the group which received the enhancer [18.12 +/- 5.43 ng ml-1 h-1 (+/- S.D.)] was higher than that in the control group (11.49 +/- 3.67 ng h-1 ml-1), t-test; p = 0.0483. Hence it was shown that administration of an enhancer could increase the oral bioavailability of diltiazem.

Effect of hydrochlorothiazide on the pharmacokinetics of enalapril in hypertensive patients with varying renal function.

An open, randomised, cross-over study was performed to investigate the pharmacokinetics of enalaprilat, administered as 20 mg enalapril both as monotherapy and in combination with hydrochlorothiazide (HCTZ 12.5 mg). Three groups of 6 hypertensive patients were enrolled [untreated diastolic blood pressure (DBP) 90-115 mm Hg]; normal renal function [glomerular filtration rate (GFR) > 81 ml min-1 1.73 m-2], mild renal impairment (GFR 51-80 ml min-1 1.73 m-2), and moderate renal impairment (GFR 31-50 ml min-1 1.73 m-2). The pharmacokinetics of enalaprilat and enalaprilat plus HCTZ correlated predictably with renal impairment with increased plasma concentrations and decreased urinary elimination at lower values of GFR. The coadministration of HCTZ had no significant effect on the pharmacokinetics of enalaprilat in any group. We conclude that although the pharmacokinetics of both enalaprilat and HCTZ are related to renal function, HCTZ has no significant effect on the pharmacokinetics of enalaprilat and that dosage adjustment for both regimens should be based on renal function.

Patient-controlled analgesia using a miniature electrochemically driven infusion pump.

We describe a miniature electrochemically driven, wrist-worn infusion pump. Generation of gas by an electrolytic reaction compresses a reservoir containing medication and provides a predictable and controllable infusion rate. The pump was used for patient-controlled analgesia (PCA) in women who required analgesia after Caesarean section. It was accepted readily and was convenient for both patients and nursing staff. This portable system, using a novel motive force, has advantages of convenience over larger systems and has sophisticated features not present in existing small systems. It has potential as a routine PCA device and it may have uses in other situations requiring convenient infusion or intermittent injection in an ambulatory setting.

Staff-staff relations group.

This article describes, through the use of clinical examples, how a staff-staff relations group functions in a brief, evening, partial-hospitalization program, and how it differs from other groups within the program. It further illustrates how the appropriate use of this group allows staff to work together harmoniously and treat patients more effectively. This article also compares and contrasts this method of dealing with staff-staff and staff-patient conflict with other approaches.

Calcium antagonists in the elderly.

The calcium antagonists are associated with a number of advantages over other antihypertensive agents, such as a lack of metabolic, vascular and respiratory adverse events, yet are effective in reducing blood pressure. The currently available calcium antagonists are widely used, and new members, particularly of the dihydropyridine group, continue to emerge. These agents may well be considered for use in the management of hypertension and angina in elderly people. They undergo significant first-pass metabolism and tend to have high values of hepatic clearance with minimal amounts of unchanged drug in the urine. Plasma concentrations tend to be higher in elderly people and for that reason it may be prudent to initiate therapy with lower dosages. With this caveat, adverse effect profiles seem to be qualitatively and quantitatively similar in younger and older people. At equivalent plasma concentrations, the antihypertensive effect appears similar in young and elderly patients, and clinical studies point to comparable efficacy with other drug classes. Calcium antagonists do not have adverse renal, respiratory, cardiovascular, metabolic or peripheral vascular effects and therefore may be useful in patients with relevant concomitant disease.

Vasodilator therapy for acute heart failure: haemodynamic comparison of hydralazine/isosorbide, alpha-adrenoceptor blockade, and angiotensin-converting enzyme inhibition.

Haemodynamic comparison of three vasodilation regimens [intravenous (i.v.) hydralazine and isosorbide dinitrate (ISDN) combined, i.v. doxazosin, and i.v. enalaprilat] was undertaken in 36 patients with acute left ventricular (LV) failure due to recent myocardial infarction. Each regimen achieved similar reductions in pulmonary artery occluded pressure (PAOP, preload) and systemic arterial pressures (afterload), with increased cardiac and stroke volume (SV) indexes (p less than 0.01). Only the hydralazine and isosorbide combination induced resting tachycardia. Balanced vasodilatation after selective alpha-adrenoceptor blockade (doxazosin) and angiotensin-converting enzyme (ACE) inhibition (enalaprilat) without increase in heart rate (HR) suggests that these therapies may have definite haemodynamic advantages over the hydralazine/ISDN combination.

Clinical pharmacokinetics of calcium antagonists. An update.

The calcium antagonists are valuable and widely used agents in the management of essential hypertension and angina. There is an increasing number of new agents to add to the 3 prototype substances nifedipine, diltiazem and verapamil. These new agents are dihydropyridines structurally related to nifedipine. However, they tend to have longer elimination half-lives (t 1/2 beta) and may be suitable for twice-daily administration. Amlodipine is an exception with a t 1/2 beta in excess of 30h. Apart from elimination rates, however, the pharmacokinetic characteristics of the newer agents have a notable tendency to resemble those of the established agents. They are highly cleared drugs, are relatively highly protein bound. As they are subject to significant first-pass metabolism, old age and hepatic impairment will increase their plasma concentrations due to a reduced first-pass effect. Renal impairment does little to their pharmacokinetics since the fraction eliminated unchanged by the kidney is small. For most agents, plasma concentration-response relationships have been described. Interesting areas for further research include chronopharmacokinetics, stereoselective pharmacokinetics and lipid solubility. Drugs affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. Some of the newer calcium antagonists will, like verapamil, increase plasma digoxin concentrations. Verapamil and diltiazem decrease phenazone (antipyrine) metabolism and therefore tend to decrease the metabolism of other drugs.

Object classification and acoustic imaging with active sonar.

The theoretical underpinnings of underwater acoustic classification and imaging using high-frequency active sonar are studied. All essential components of practical classification systems are incorporated in a Bayesian theoretic framework. The optimum decision rules and array processing are presented and evaluated. A systematic performance evaluation methodology is derived. New results quantify the relationship between classifier performance and object geometry, acoustic imaging, and the accuracy of a priori knowledge infused into the processor.

Nitrates in the elderly. Pharmacological considerations.

Although a significant proportion of patients receiving nitrates are elderly, surprisingly little published work is available describing the pharmacokinetics and pharmacodynamics of these agents in elderly patients. The lack of pharmacokinetic data is related to the difficulty in assaying nitrates and there are at present no definitive data describing the effect of aging on their bioavailability or elimination. A common finding in old age is of decreased hepatic first-pass metabolism. This would affect isosorbide-2-mononitrate and isosorbide-5-mononitrate less than isosorbide dinitrate and nitroglycerin (glyceryl trinitrate). Venous responsiveness to nitrates does not appear to alter with age, so that pharmacodynamic properties would not be expected to alter. However, decreased baroreflex function causes an increased tendency for posturally related side effects to occur. Mechanisms of tolerance are likely to be unaltered but any possible alteration in quantitative aspects of tolerance has not been studied. Nitrate therapy in the elderly would benefit from systematic investigation. At the moment, therapy needs to be titrated to the individual patient, with care taken to avoid age-related side effects by careful initiation of therapy and appropriate reviews of each patient.

Pharmacokinetic properties and antihypertensive efficacy of once-daily diltiazem.

The pharmacokinetic and clinical characteristics of a once-daily formulation of diltiazem are described. In a 20 subject, 5 day, steady-state pharmacokinetic study, 120 and 240 mg of once-daily diltiazem were bioequivalent on a dose-adjusted basis and were bioequivalent to a conventional reference product administered four times daily. The conventional formulation showed marked diurnal variation in its pharmacokinetics. Plasma concentrations following its administration at 2100 and 0300 h were significantly lower than following administration at 0900 and 1500 h. One hundred forty-four hypertensive patients completed a 16 week placebo-controlled, dose-titrated study examining the effects of once-daily diltiazem at doses of 120, 240, and 360 mg. Blood pressure was measured manually and (in 121 patients) by ambulatory evaluation. Following dose titration, diltiazem given once daily reduced blood pressure with significant effects present at 24 h following drug administration. Ambulatory blood pressures were lower than those measured manually and data from the manual measurements demonstrated a placebo effect suggested to result primarily from investigator bias. The placebo-adjusted reduction in blood pressure 24 h following a dose of diltiazem was approximately 5 mm Hg and was comparable for manual (supine and standing) and ambulatory measurements. Diltiazem was well tolerated. The only significant findings were of tiredness/dizziness (9 patients of 144) or oedema (also 9 of 144). The incidence of headache was not different than placebo. On both pharmacokinetic and pharmacodynamic grounds, the results indicate that diltiazem can be formulated in a manner suitable for once-daily antihypertensive use.