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PubMed2002

Mobilization and entry of DNAPL pools into finer sand media by cosolvents: two-dimensional chamber studies.

Two-dimensional chamber studies were conducted to determine qualitative and quantitative performance of cosolvents targeted at pooled dense non-aqueous phase liquid (DNAPL) (perchlorethylene, PCE) residing above a fine-grain capillary barrier. Downward mobilization of DNAPL, up gradient along an overriding cosolvent front, was observed. This produced significant pooling above a fine-grain layer that in some cases lead to entry into the capillary barrier beneath. Entry pressure calculations using physical and hydrogeologic parameters provided an excellent prediction of breakthrough of DNAPL into the capillary barrier. Calculations predict approximately 0.5 m of DNAPL would be necessary to enter a Beit Netofa clay, under extreme cosolvent flooding conditions (100% ethanol). Gradient injection of cosolvent did not appear to provide any benefit suggesting a rapid decrease in interfacial tension (IFT) compared to the rate of DNAPL solubilization. Use of a partitioning alcohol (tertiary butyl alcohol, TBA) resulted in DNAPL swelling and reduced entry into the capillary barrier. However, the trapping of flushing solution, containing PCE, could potentially lead to longer remediation times.

Benzenesulfonates↗
PubMed2000

Evolving concepts in the pathogenesis of chronic obstructive pulmonary disease.

It is arguable that more biologic insight has been gained from the study of COPD than from any other pulmonary disorder. A vast knowledge of the biology of extracellular matrix proteins, proteinases, and proteinase inhibitors has largely stemmed from the elastase:anti-elastase hypothesis for the pathogenesis of emphysema. An equally compelling case could be made that interest in, and funding for, COPD research has been woeful, and investigators have made no significant medical breakthroughs in the treatment of this disorder, which, unfortunately, is becoming epidemic worldwide. Indeed, it cannot be argued that physicians have very little treatment to offer to the many patients with COPD. Humankind is rapidly approaching a time when all human genes will be sequenced, and genetic engineering will allow determination of the function of these proteins in vivo. Expression profiling and bioinformatics will allow clinicians to assess the spectrum of genes and proteins regulated in biologic processes, no longer limiting study to naïve candidate genes. These advances will allow investigators to decipher precise pathways of complex diseases, identify genetic and environmental interactions, and ultimately lead to specific (pre)diagnoses and rational treatment. Answers to the question as to why only a subset of smokers develop COPD will enhance the understanding of the disease process. Fortunately, there has been a resurgence of interest in COPD, led largely by the pharmaceutical industry, which has discovered the potential of this unmet need. Consequently, these state-of-the-art scientific techniques are being directly applied to COPD, lending hope for the future. Of even greater importance, the tide seems to be turning on the cigarette industry. Although difficult to imagine, perhaps cigarettes will disappear in this lifetime or at least the next generation won't be fooled by this deadly habit! Well ... the rational therapy thing could work.

Airway Obstruction↗
PubMed1993

Immunization and immunotherapy for mastitis.

Immunization and immunotherapy for mastitis are active areas of investigation. The past decade has seen development of effective and economical R-mutant vaccines for gram-negative mastitis. These vaccines doubtless will prove beneficial on well managed dairies that have eradicated contagious mastitis pathogens. Development of vaccines for other mastitis pathogens has been noticeably slower. A commercially available Staphylococcus aureus vaccine appears to reduce the frequency and severity of clinical episodes, but probably has minimal impact on the incidence or prevalence of infection. This product has not been extensively studied. The recent recognition of virulence factors produced in vivo by Staphylococcus aureus may provide a breakthrough in the development and production of Staphylococcus aureus vaccines. Bacterins employing this principle presently are not commercially available, however. In the case of all contagious mastitis pathogens (Streptococcus agalactiae, Staphylococcus aureus, and Mycoplasma spp.), traditional control and eradication efforts (teat dip, dry cow therapy, culling programs) likely will prove preferable to long-term immunization. Ongoing research may provide more efficacious vaccines for these mastitis syndromes. Immunostimulants are an active area of research. Although leukopoietic factors appear promising as immunostimulants, no compound has clearly demonstrated efficacy in either the prevention or treatment of bovine mastitis.

Animals↗
PubMed2004

Pharmacokinetic interactions of drugs with St John's wort.

There is a worldwide increasing use of herbs which are often administered in combination with therapeutic drugs, raising the potential for herb-drug interactions. St John's wort (Hypericum perforatum) is one of the most commonly used herbal antidepressants. A literature search was performed using Medline (via Pubmed), Biological Abstracts, Cochrane Library, AMED, PsycINFO and Embase (all from their inception to September 2003) to identify known drug interaction with St John's wort. The available data indicate that St John's wort is a potent inducer of CYP 3A4 and P-glycoprotein (PgP), although it may inhibit or induce other CYPs, depending on the dose, route and duration of administration. Data from human studies and case reports indicate that St John's wort decreased the blood concentrations of amitriptyline, cyclosporine, digoxin, fexofenadine, indinavir, methadone, midazolam, nevirapine, phenprocoumon, simvastatin, tacrolimus, theophylline and warfarin, whereas it did not alter the pharmacokinetics of carbamazepine, dextromethorphan, mycophenolic acid and pravastatin. St John's wort decreased the plasma concentration of the active metabolite SN-38 in cancer patients receiving irinotecan treatment. St John's wort did not alter the pharmacokinetics of tolbutamide, but increased the incidence of hypoglycaemia. Several cases have been reported that St John's wort decreased cyclosporine blood concentration leading to organ rejection. St John's wort caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when coadministered with selective serotonin-reuptake inhibitors (e.g. sertaline and paroxetine). Both pharmacokinetic and pharmacodynamic components may play a role in these interactions. Because the potential interaction of St John's wort with other drugs is a major safety concern, additional systematic research on herb-drug interactions and appropriate regulation in herbal safety and efficacy is needed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1981

[The current state of curability of Hodgkin's disease].

The introduction of the chemotherapy regimen MOPP in 1964 led to a breakthrough in the treatment of disseminated Hodgkin's disease. 80% of previously untreated patients achieve complete remission which in the majority of cases is durable. However, in view of prolonged survival in an increasing number of patients, more secondary malignancies (acute myelogenous leukemia and non-Hodgkin's lymphoma) are observed. The problem of how to treat patients who fail to respond to MOPP is still unsolved. Alternating use of two chemotherapy regimens and additional radiotherapy may further diminish the incidence of relapses in patients who have achieved complete remission. Stage II Hodgkin's disease probably should be divided into two substages requiring different treatment.

Chromosome Aberrations↗
PubMed1996

Hepatitis A: from epidemic jaundice to a vaccine-preventable disease.

Hepatitis A probably causes an identifiable illness in less than 5% of individuals who are infected with the virus. Nonetheless, it has been an important cause of morbidity throughout history. Hepatitis A remains endemic in some developing nations, and cyclical epidemics still occur in developed nations, including the United States. Because infections are less common in children in developed nations, the pattern of infection has shifted toward older age groups. This shift is a concern because the disease tends to be far more symptomatic in older patients, and more than 70% of reported deaths are among persons older than 49 years of age. Hepatitis A does not cause chronic disease, but atypical presentations associated with a relapse may persist for several months. Although the risk of infection can be significantly reduced by adhering to good sanitary precautions, these precautions are not always practiced in certain environments, and there is a need for a universal immunization strategy. Passive immunization with pooled immune serum globulin is effective when administered within 2 to 3 weeks of exposure. Unfortunately, the window of opportunity is often missed because the majority of cases of hepatitis A have no history of exposure. The effectiveness of immune serum globulin is also short-lived. An effective breakthrough in prevention occurred with the development of a killed vaccine, which has proven to be effective for active immunization. It was licensed in the United States in 1995.

Hepatitis A↗
PubMed2002

Decremental intravenous pulse propagation during extrastimulus pacing: relevance for catheter ablation of focal atrial fibrillation.

We report a case study demonstrating delayed circumferential intrapulmonary-venous conduction characteristics during coronary sinus extrastimulus pacing. This phenomenon allowed the unmasking and discrimination of a localized left atrial to PV breakthrough from secondarily activated PV muscle in a common left-sided PV ostium. Thus, this pacing manoeuvre may serve to guide RF delivery in the treatment of focal AF.

Atrial Fibrillation↗
PubMed2005

[Cytological method of diagnosis of breakthrough bleeding].

The studies have been carried out by means of analysis of cytological diagnoses made during the assessment of uterobrush preparations of the endometrium. Cytological material has been sampled in the case of pathological bleeding of low intensity. Glandular hyperplasia occurred in 18% of cases, cancer in about 1%, inflammatory process in 11%. The comparison of received data with the results of histological examinations of scrapings from the uterine cavity does not show any significant differences. The authors think that the cytological method of diagnosing a pathological state of endometrium is credible.

Adult↗
PubMed1999

Pneumocystis carinii severe pneumonia among human immunodeficiency virus-infected children in Thailand: the effect of a primary prophylaxis strategy.

BACKGROUND: A knowledge of the epidemiology of Pneumocystis carinii pneumonia (PCP) is important for the development of a strategy for primary PCP prophylaxis and empiric treatment for severe pneumonia in HIV-infected children. However, little is known about the epidemiology of PCP in developing countries. Objective. To measure the relative rate of PCP among hospitalized HIV-infected children with severe pneumonia in Bangkok and evaluate the effect of a strategy of primary PCP prophylaxis in HIV-exposed infants. METHODS: All HIV-infected children hospitalized from January, 1996, to December, 1997, for severe pneumonia were investigated for PCP with the use of specimens obtained from bronchoalveolar lavage, endotracheal aspiration or lung tissue necropsy. Characteristics associated with severe pneumonia were described, and the differences between PCP and non-PCP in these severely ill children were analyzed. In June, 1996, a strategy of primary PCP prophylaxis using trimethoprim-sulfamethoxazole in all HIV-exposed infants from 1 to 6 month of age was initiated in our institution. The effect of this strategy was evaluated. RESULTS: Of 279 hospitalized HIV-infected children 128 (46%) were diagnosed with pneumonia and 26 (20%) of these had severe pneumonia. P. carinii was identified in 9 (35%) children with severe pneumonia. After June, 1996, the rate of severe pneumonia among all hospitalized children decreased from 16% from January through June, 1996, to 7% from July, 1996, through December, 1997 (P = 0.02). Cases of PCP decreased from 9 in 1996 to zero in 1997. The percentage of HIV-infected children receiving PCP prophylaxis at the time of admission increased from 53% before June, 1996, to 72% in late 1997 (P = 0.04). The overall percentage of patients with severe pneumonia receiving PCP prophylaxis at the time of admission was 34%. Breakthrough PCP occurred in 2 children with poor compliance. Patients with PCP were significantly younger than those without PCP (mean age, 10.6+/-10.6 vs. 29.8+/-28.3 months, P = 0.02). CONCLUSION: PCP occurred in one-third of cases of severe pneumonia in HIV-infected children in Bangkok. The data suggest that PCP prophylaxis can prevent both PCP and non-PCP.

AIDS-Related Opportunistic Infections↗
PubMed2004

A case study of successful patient flow methods: St. John's Hospital.

Participating in the Institute for Healthcare Improvement (IHI) IMPACT collaborative has given St. John's Hospital the opportunity to improve patient flow and the delivery of patient care. This partnership has allowed us to experience a wealth of information shared by a collaborative network of hospitals. IHI has introduced rapid-cycle improvement methodologies, variability-reduction strategies, and strategies to aid in planning for the expected as methods that have enhanced our already established performance-improvement program. St John's has achieved breakthrough improvement with patient flow.

Academies and Institutes↗
PubMed2003

Postbreakthrough behavior in flow through porous media.

We numerically simulate the traveling time of a tracer in convective flow between two points (injection and extraction) separated by a distance r in a model of porous media, d=2 percolation. We calculate and analyze the traveling time probability density function for two values of the fraction of connecting bonds p: the homogeneous case p=1 and the inhomogeneous critical threshold case p=p(c). We analyze both constant current and constant pressure conditions at p=p(c). The homogeneous p=1 case serves as a comparison base for the more complicated p=p(c) situation. We find several regions in the probability density of the traveling times for the homogeneous case (p=1) and also for the critical case (p=p(c)) for both constant pressure and constant current conditions. For constant pressure, the first region I(P) corresponds to the short times before the flow breakthrough occurs, when the probability distribution is strictly zero. The second region II(P) corresponds to numerous fast flow lines reaching the extraction point, with the probability distribution reaching its maximum. The third region III(P) corresponds to intermediate times and is characterized by a power-law decay. The fourth region IV(P) corresponds to very long traveling times, and is characterized by a different power-law decaying tail. The power-law characterizing region IV(P) is related to the multifractal properties of flow in percolation, and an expression for its dependence on the system size L is presented. The constant current behavior is different from the constant pressure behavior, and can be related analytically to the constant pressure case. We present theoretical arguments for the values of the exponents characterizing each region and crossover times. Our results are summarized in two scaling assumptions for the traveling time probability density; one for constant pressure and one for constant current. We also present the production curve associated with the probability of traveling times, which is of interest to oil recovery.

Journal Article↗
PubMed1991

Treatment of AIDS with combinations of antiretroviral agents.

Although 3'-azido-3'-deoxythymidine (zidovudine, AZT) has demonstrated efficacy in the treatment of human immunodeficiency virus (HIV) infection, there are limitations associated with its use. Consequently, other agents, such as 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI), are being assessed for the treatment of patients with HIV infection. However, the most effective therapy for HIV infection may be combination therapy with zidovudine and any of a number of other therapies. To obtain maximum efficacy, combination regimens should include agents that do not share cross-resistance, have different mechanisms of action, and have different dose-limiting toxicities; the relative merits of a concurrent dosage schedule (limits drug failure) and a consecutive dosage schedule (limits toxicity) must also be considered. In addition, the shift between administering a starting regimen and a rescue regimen should be based on time on therapy, disease breakthrough, or drug complication. Eventually, the shift may be precipitated by the in vitro resistance patterns of individual viruses, as is now the case with antibiotics for infection. Several trials are currently in progress to assess combination therapy with zidovudine and ddC; initial results indicate that the combination may allow for improved efficacy and decreased side effects, compared with treatment with either drug alone. Trials of combination therapy with ddI, interferon alfa, and acyclovir are also in progress. It is hoped that these initial studies will pave the way for rational drug sequencing in the treatment of patients with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Cerebral blood flow imaging in arteriovenous malformation complicated by normal perfusion pressure breakthrough.

BACKGROUND: A patient with normal perfusion pressure breakthrough (NPPB) after surgical removal of an arteriovenous malformation (AVM) was evaluated using single photon emission computed tomography cerebral blood flow (CBF) imaging. CASE DESCRIPTION: A 48-year-old man suffered consciousness disturbance because of an intraventricular hemorrhage and underwent ventricular drainage. Cerebral angiography showed a medium-sized AVM in the left parietal lobe. Three months after the ictus, a left parietal craniotomy was performed and total removal of the AVM was achieved. A brain region adjacent to the AVM with preoperative decreased vasoreactivity to acetazolamide showed marked hyperperfusion after AVM excision. Hemorrhage subsequently occurred in this area. CONCLUSION: CBF mapping seems to offer a noninvasive method for the preoperative identification of AVM patients at risk for NPPB, and to allow for early postoperative diagnosis of NPPB.

Blood Flow Velocity↗
PubMed2002

Bacteremias caused by Escherichia coli in cancer patients - analysis of 65 episodes.

OBJECTIVES: The aims of this study were to evaluate risk factors, clinical presentation, outcome and antimicrobial susceptibility in patients with Escherichia coli bacteremia occurring over seven years in a single cancer hospital. METHODS: Sixty five episodes of bacteremia from E. coli appearing over seven years from 12,301 admissions in a single cancer institution were retrospectively analyzed. RESULTS: The proportion of bacteremia caused by E. coli among Gram-negative bacteremia was 20.8% (the second most common organism after Pseudomonas aeruginosa), and infection-associated mortality was 17%. The incidence in 1989-1995 varied from 14.3 to 24.7%. The most common risk factors were: solid tumors as the underlying disease (70.7%); central venous catheter insertion (32.3%); prior surgery (46.2%), and prior chemotherapy within 48 h (44.4%). Neutropenia and urinary catheters did not place patients at high risk in any of the subgroups. When we compared the two subgroups of 61 cases of bacteremia - monomicrobial and polymicrobial (when E. coli was isolated from blood culture with another microorganism) - we found that acute leukemia and breakthrough (recurrence while receiving antibiotics) bacteremia were more frequently associated with polymicrobial E. coli bacteremia. There was also a difference in infection-associated mortality: monomicrobial bacteremia due to E. coli only had a significantly lower mortality in comparison with polymicrobial E. coli bacteremia (8.9 vs 35.0%, respectively; P<0.03). CONCLUSION: The susceptibility of 115 E. coli strains isolated from 65 episodes of bacteremia was stable. Only two episodes caused by quinolone-resistant strains occurred, both in 1995, after six years of using ofloxacin for prophylaxis in neutropenic patients in our hospital. We found that 85.2-91.3% of all strains were susceptible to aminoglycosides, 97.8% to quinolones, and 90-100% to third generation cephalosporins and imipenems. The patients most commonly infected had solid tumors and the mortality was only 17%.

Anti-Bacterial Agents↗
PubMed2004

Experimental visualization of solute transport and mass transfer processes in two-dimensional conductivity fields with connected regions of high conductivity.

Solute transport displaying mass transfer behavior (i.e., tailing) occurs in many aquifers and soils. Spatial patterns of hydraulic conductivity may play a role because of both advection and diffusion through isolated low conductivity areas. We demonstrated such processes in laboratory experiments designed to visualize solute transport through a thin chamber (40 cm x 20 cm x 0.64 cm thick) packed with glass beads and containing circular emplacements of smaller glass beads with lower conductivity. The experiments used three different contrasts of conductivity between the large-bead matrix and the emplacements, targeting three different regimes of solute transport: low contrast, targeting macrodispersion; intermediate contrast, targeting advection-dominated mass transfer between the high-conductivity regions and the emplacements; and high contrast, targeting diffusion-dominated mass transfer. Use of a strong light source, a high-resolution CCD camera, and a colorimetric dye produced images with a spatial resolution of about 400 microm and a concentration range of approximately 2 orders of magnitude. These images confirm the existence of the three different regimes, and we observed tailing driven by both advection and diffusion. Outflow concentration measured by spectrophotometer achieved 3 orders of magnitude in concentration range and showed good agreement with known models in the case of dispersion and diffusive mass transfer, with estimated parameters close to a priori predictions. Existing models for diffusive mass transfer did notfitthe breakthrough curves from the intermediate-contrast chamber, but a model of slow advection through cylinders did. Thus, both breakthrough curves and chamber images confirm that different contrasts in small-scale K lead to different regimes of solute transport and thus require different models of upscaled solute transport.

Models, Theoretical↗
PubMed1997

History of clinical research on the sleep apnea syndrome. The early days of polysomnography.

This article gives a brief historical overview of the literature on the sleep apnea syndrome (SAS), including initial case reports of the Pickwickian syndrome and its treatment with tracheostomy. It also highlights the beginnings of early clinical neurophysiology and describes the breakthrough in the understanding of the pathophysiology of SAS by performing polysomnography.

History, 19th Century↗
PubMed1998

Responsibility for clinical innovation. A case study in neonatal medicine.

Proper evaluation of clinical innovations and of the process of their diffusion is essential for the development of sound health care policy. This case study examines transcutaneous oxygen monitoring in neonatal intensive care, a procedure that was rapidly adopted in the late 1970s as a scientific breakthrough of great promise, then all but abandoned within a decade in favor of pulse oximetry, a still more recent technology. The study incorporates the results of interviews with representatives of industry as well as biomedical researchers and clinicians involved with these devices. Factors in technology diffusion are analyzed, with special attention to those susceptible to change by policy makers. Participants in the diffusion process also include nurses, hospital administrators, the legal profession, the news media, and the public, but the pivotal role--and hence ultimate responsibility--is seen to be that of the physician. The discussion is presented in the context of a proposed "ethics of evidence" pertinent to medical decision making.

Attitude of Health Personnel↗