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Polyherbal formulations with wide spectrum antimicrobial activity against reproductive tract infections and sexually transmitted pathogens.

PROBLEM: Recent reports indicate high incidence of genital infections, most of which are sexually transmitted. Although specific drugs and antibiotics are available for some, a safe spermicidal formulation with wide spectrum antimicrobial action would be a desirable addition to the presently available spermicides. METHODS: Formulations at different dilutions were tested in culture systems on standard strains and clinical isolates including some isolates resistant to drugs. The effect on (HSV)-2 and Chlamydia trachomatis was determined in vivo in progestin sensitized mice. The effect on HIV-1 was investigated in two standardized systems. RESULTS: Polyherbal cream inhibited the growth in culture of clinical isolates of Candida albicans, Candida krusei and Candida tropicalis. Both the polyherbal cream and the Praneem polyherbal pessary inhibited urinary tract Escherichia coli (including multidrug resistant strains), and Neisseria gonorrhoeae (including 2 strains resistant to penicillin). Both formulations manifested virucidal activity against HIV-1 at >2 and 50% dilutions (in two different test systems) on contact for 1-2 min. Intravaginal inoculation of the cream and the pessary suspensions before inoculation of the pathogen prevented lesions and vaginal transmission of HSV-2 and C. trachomatis in progestin sensitized mice. CONCLUSIONS: Polyherbal formulations have wide spectrum antibacterial, antifungal and antiviral effect against the tested sexually transmitted pathogens.

Animals↗

The need for epidemiological research in road trauma.

This paper discusses the application of epidemiological methods to the public health problem of road trauma. The complex nature of the system is stressed, and some consequent difficulties in the formulation of appropriate hypotheses are outlined. Examples are given. To solve these problems, the paper proposes the formation of multidisciplinary full-time epidemiological research teams.

Accidents, Traffic↗

Levodopa infusion therapy in Parkinson disease: state of the art in 2004.

Orally administered levodopa, in combination with a decarboxylase inhibitor, is the gold standard therapy for Parkinson disease (PD). The problems in management of motor fluctuations in the advanced stages of the disorder are due to the close relationship between plasma levodopa levels and availability of dopamine at striatal receptor sites. The fluctuating levodopa concentrations are mainly explained by the fact that levodopa absorption only occurs in the proximal small intestine. The patient's motor function thus depends on gastric emptying, which is erratic and may even be delayed in PD. Oral therapy with sustained-release formulations and COMT inhibitors have not solved the problems satisfactorily. Therefore, infusions of levodopa by intravenous and enteral (duodenal/jejunal) routes of administration have been studied. In this review of the literature on clinically relevant levodopa infusion studies, it is shown that improvements regarding fluctuations in both plasma levodopa levels and motor performance have been repeatedly reported. The results acquired so far suggest that levodopa infusion is a safe and efficacious therapy. Recent drug delivery development and long-term studies have shown that infusion is a clinically feasible alternative to treat advanced PD.

Adult↗

The dyslexia-emotional dyad: implications for diagnosis and treatment.

Extensive experience with dyslexic children indicates that developmental language problems and emotional problems represent a dyad rather than a dichotomy. An attempt is made to place this complex and extensive problem into meaningful perspective. When accurate diagnosis and carefully formulated treatment plans are effectively blended, success in helping these often hapless children is greatly enhanced. Some important guidelines, derived from clinical experiences, are indicated to be valuable in understanding and helping patients with these multi-faceted problems.

Adolescent↗

Absolute conductivity reconstruction in magnetic induction tomography using a nonlinear method.

Magnetic induction tomography (MIT) attempts to image the electrical and magnetic characteristics of a target using impedance measurement data from pairs of excitation and detection coils. This inverse eddy current problem is nonlinear and also severely ill posed so regularization is required for a stable solution. A regularized Gauss-Newton algorithm has been implemented as a nonlinear, iterative inverse solver. In this algorithm, one needs to solve the forward problem and recalculate the Jacobian matrix for each iteration. The forward problem has been solved using an edge based finite element method for magnetic vector potential A and electrical scalar potential V, a so called A, A - V formulation. A theoretical study of the general inverse eddy current problem and a derivation, paying special attention to the boundary conditions, of an adjoint field formula for the Jacobian is given. This efficient formula calculates the change in measured induced voltage due to a small perturbation of the conductivity in a region. This has the advantage that it involves only the inner product of the electric fields when two different coils are excited, and these are convenient computationally. This paper also shows that the sensitivity maps change significantly when the conductivity distribution changes, demonstrating the necessity for a nonlinear reconstruction algorithm. The performance of the inverse solver has been examined and results presented from simulated data with added noise.

Algorithms↗

Proof of concept: performance testing in models.

Pharmacokinetic (PK) and pharmacodynamic (PD) principles that predict antimicrobial efficacy can be used to set targets for antimicrobial design and optimisation. Although current formulations of amoxicillin and amoxicillin/clavulanate have retained their efficacy against many, but not all, penicillin-nonsusceptible Streptococcus pneumoniae, additional coverage is required to address the growing problem of drug-resistant strains. Accordingly, two new oral formulations of amoxicillin/clavulanate, a paediatric formulation at 90/6.4 mg/kg/day and a pharmacokinetically enhanced formulation at 2000/125 mg twice daily for adults, were designed using PK/PD principles. These principles indicate that for amoxicillin and amoxicillin/clavulanate, a time above MIC of 35-40% of the dosing interval is predictive of high bacterial efficacy. In line with PK/PD predictions, simulation of human pharmacokinetics in in-vitro kinetic models and in a rat model of pneumonia, amoxicillin/clavulanate 2000/125 mg twice daily was highly effective against S. pneumoniae strains with amoxicillin MICs of 4 or 8 mg/L. Against strains with amoxicillin MICs of 4 mg/L, amoxicillin/clavulanate 2000/125 mg twice daily was significantly more effective than the conventional 875/125 mg twice daily formulation, azithromycin and levofloxacin, even though all levofloxacin MICs were < or = 1 mg/L. Following infection with S. pneumoniae strains with amoxicillin MICs of 8 mg/L, the amoxicillin/clavulanate 2000/125 mg twice daily formulation was more effective than the conventional amoxicillin/clavulanate formulations of 875/125 mg twice daily and three times daily and 1000/125 mg three times daily, and had similar or better efficacy than azithromycin and levofloxacin, depending on the strain. These data indicate the potential benefit of therapy with amoxicillin/clavulanate 2000/125 mg twice daily compared with conventional formulations and other marketed antimicrobials in the treatment of respiratory tract infection.

Amoxicillin-Potassium Clavulanate Combination↗

Long-lasting effects of a Bacillus thuringiensis serovar israelensis experimental tablet formulation for Aedes aegypti (Diptera: Culicidae) control.

Dengue is a growing public health problem in many tropical and subtropical countries worldwide. At present, the only method of controlling or preventing the disease is to eliminate its vector, Aedes aegypti (L.) (Diptera: Culicidae). In the current study, an experimental larvicide tablet formulation XL-47 based on Bacillus thuringiensis serovar israelensis (Bti) and containing 4.8% of technical powder was developed. This formulation was evaluated against Ae. aegypti in three different sets of experiments, under field-simulated conditions: two experiments were indoors and under partial sunlight exposure and one experiment was outdoors with sunlight exposure. Larvae were added throughout the experiment two times per week, and the residual larvicidal activity was recorded daily. Pupal formation was reduced in the containers with Bti by > 80% in relation to the containers without treatment for 12 wk; to our knowledge, this is the longest period of control reported for a Bti tablet formulation outdoors under sunlight exposure. Moreover, samples from the top, middle, and bottom of the water column were collected to perform bacterial plate counts and toxicity assays. The Bti population and the active ingredient of the tablet formulation remained mainly at the bottom of the containers and mosquito larvae reached the formulation by diving and shredding the tablet's material. In conclusion, the experimental tablet formulation XL-47 showed an inhibition of pupal formation that lasted for long periods under sunlight exposure.

Aedes↗

[Information systems in epidemiology].

At present epidemiological informations are dispatched from epidemiological departments of regional hygiene stations in different forms to different departments. The separate follow up of partial information leads to the development of different isolated information systems. Individual information systems help to resolve information problems in epidemiology, they provide, however, only limited opportunities when causal relations are sought and applied in the control of diseases. Surveillance calls for a uniform information system which concentrates scattered information in a single epidemiological centre. The author formulates possible approaches to the solution of the information problem in epidemiology.

Epidemiology↗

Skin benefits from continuous topical administration of a zinc oxide/petrolatum formulation by a novel disposable diaper.

BACKGROUND: Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have advanced in our development of a novel diaper that delivers dermatological formulations to help protect the skin from over-hydration and irritation. OBJECTIVE: To determine the clinical benefits of a novel disposable diaper designed to deliver a zinc oxide and petrolatum-based formulation continuously to the skin during use. METHODS: All studies were independent, blinded, randomized clinical trials. Study A was conducted to confirm transfer of the zinc oxide/petrolatum (ZnO/Pet) formulation from the diaper to the child's skin during use. Children wore a single diaper for 3 h or multiple diapers for 24 h. After the use period, stratum corneum samples were taken from each child and analysed for ZnO/Pet. Study B evaluated the prevention of skin irritation and barrier damage from a standard skin irritant (SLS) in an adult arm model. Study C evaluated skin erythema and diaper rash in 268 infants over a 4-week usage period. One half of the infants used the ZnO/Pet diaper, while the other half used a control diaper that was identical except for the absence of the ZnO/Pet formulation. RESULTS: The ointment formulation and ZnO transferred effectively from the diaper to the child's skin during product use. Transfer of ZnO increased from 4.2 microg/cm2 at 3 h to > 8 microg/cm2 at 24 h. Exposure to the formulations directly on adult skin prior to an irritant challenge was associated with up to a 3.5 reduction in skin barrier damage and skin erythema. Greatest reductions were seen for the ZnO containing formulations. Wearing of the formulation treated diaper was also associated with a significant reduction in skin erythema and diaper rash compared to the control product. CONCLUSIONS: The results demonstrated the clinical benefits associated with continuous topical administration of a zinc oxide/petrolatum-based formulation by this novel diaper.

Administration, Topical↗

Allergy and the contemporary laryngologist.

The author believes that allergy plays an important role in the field of laryngology. Not every patient has significant allergic problems, but the allergic factor in laryngeal problems should not be underestimated. The insights and technology for research have never been better. Many cause-and-effect relationships have been suggested and often provide the working basis for current therapeutics. Many current models of operation need to be verified, explored further, and modified through research. It is hoped that new technologies will achieve a higher degree of sensitivity without sacrificing specificity. Better specificity is particularly needed in allergy testing and in testing thyroid and pulmonary function. The author hopes that the contemporary laryngologist/otolaryngologist will use this overview to formulate a complete and orderly approach to laryngeal problems. Because of the complexity of laryngeal problems, referral to other specialists may be necessary. The laryngologist, however, should be able to orchestrate the appropriate use of technologies and health care specialists to address these problems.

Angioedema↗

GIST: an interactive, GPU-based level set segmentation tool for 3D medical images.

While level sets have demonstrated a great potential for 3D medical image segmentation, their usefulness has been limited by two problems. First, 3D level sets are relatively slow to compute. Second, their formulation usually entails several free parameters which can be very difficult to correctly tune for specific applications. The second problem is compounded by the first. This paper describes a new tool for 3D segmentation that addresses these problems by computing level-set surface models at interactive rates. This tool employs two important, novel technologies. First is the mapping of a 3D level-set solver onto a commodity graphics card (GPU). This mapping relies on a novel mechanism for GPU memory management. The interactive rates level-set PDE solver give the user immediate feedback on the parameter settings, and thus users can tune free parameters and control the shape of the model in real time. The second technology is the use of intensity-based speed functions, which allow a user to quickly and intuitively specify the behavior of the deformable model. We have found that the combination of these interactive tools enables users to produce good, reliable segmentations. To support this observation, this paper presents qualitative results from several different datasets as well as a quantitative evaluation from a study of brain tumor segmentations.

Algorithms↗

Adaptation problems with nursing home application for elderly persons: an application of the Roy adaptation nursing model.

This study sought to identify adaptation problems on the part of elderly persons and significant others that were associated with nursing home applications for elderly persons. Within the framework of the Roy Adaptation Nursing Model, an ex post facto research design was utilized to identify these adaptation problems. The four adaptive modes in this model are: physiological, self-concept, role function, and interdependence. The study group (n = 22) and a control group of elderly persons living in Calgary, as well as their significant others, were administered a structured questionnaire. Five hypotheses relating to overall adaptation problems, powerlessness, role reversal, guilt, and knowledge and utilization of services were formulated and tested. Only the hypothesis indicating role reversal on the part of the significant others was accepted. Adaptation problems encountered by the elderly which were associated with nursing home applications occurred in the self-concept and interdependence adaptive modes. The adaptation problems perceived by the significant others, which were associated with nursing home applications for their elderly, occurred in the self-concept, role function, and interdependence modes. Adaptation problems from the significant others' perception rather than from the elderly persons' perception appear to be more significantly associated with nursing home applications.

Adaptation, Psychological↗

Finite-Difference Time-Domain Simulator for Half-Space Bioacoustic Problems.

The finite-difference time-domain (FDTD) method provides a numerical technique for solving acoustic forward problems. The FDTD is particularly useful in geometries that encompass heterogeneities. Plane-wave modeling permits the simulation of many practical bioacoustic problems because the phase front in the focal zone of many acoustic transducers is nearly planar. The formulation presented in this paper provides a technique for solving half-space problems under local plane-wave illumination.

Journal Article↗

Integrating conflict analysis and consensus reaching in a decision support system for water resource management.

The importance of shared decision processes in water management derives from the awareness of the inadequacy of traditional--i.e. engineering--approaches in dealing with complex and ill-structured problems. It is becoming increasingly obvious that traditional problem solving and decision support techniques, based on optimisation and factual knowledge, have to be combined with stakeholder based policy design and implementation. The aim of our research is the definition of an integrated decision support system for consensus achievement (IDSS-C) able to support a participative decision-making process in all its phases: problem definition and structuring, identification of the possible alternatives, formulation of participants' judgments, and consensus achievement. Furthermore, the IDSS-C aims at structuring, i.e. systematising the knowledge which has emerged during the participative process in order to make it comprehensible for the decision-makers and functional for the decision process. Problem structuring methods (PSM) and multi-group evaluation methods (MEM) have been integrated in the IDSS-C. PSM are used to support the stakeholders in providing their perspective of the problem and to elicit their interests and preferences, while MEM are used to define not only the degree of consensus for each alternative, highlighting those where the agreement is high, but also the consensus label for each alternative and the behaviour of individuals during the participative decision-making. The IDSS-C is applied experimentally to a decision process regarding the use of treated wastewater for agricultural irrigation in the Apulia Region (southern Italy).

Agriculture↗

Bohmian dynamics on subspaces using linearized quantum force.

In the de Broglie-Bohm formulation of quantum mechanics the time-dependent Schrodinger equation is solved in terms of quantum trajectories evolving under the influence of quantum and classical potentials. For a practical implementation that scales favorably with system size and is accurate for semiclassical systems, we use approximate quantum potentials. Recently, we have shown that optimization of the nonclassical component of the momentum operator in terms of fitting functions leads to the energy-conserving approximate quantum potential. In particular, linear fitting functions give the exact time evolution of a Gaussian wave packet in a locally quadratic potential and can describe the dominant quantum-mechanical effects in the semiclassical scattering problems of nuclear dynamics. In this paper we formulate the Bohmian dynamics on subspaces and define the energy-conserving approximate quantum potential in terms of optimized nonclassical momentum, extended to include the domain boundary functions. This generalization allows a better description of the non-Gaussian wave packets and general potentials in terms of simple fitting functions. The optimization is performed independently for each domain and each dimension. For linear fitting functions optimal parameters are expressed in terms of the first and second moments of the trajectory distribution. Examples are given for one-dimensional anharmonic systems and for the collinear hydrogen exchange reaction.

Journal Article↗