Although it is reported that other transporters including.

This may be especially important for drugs such as cimetidine, where high drug concentrations have been associated with serious neurotoxicity, especially in patients with renal deficiency. Investigations of renal P-gp computing machine software and drug interactions in humans are limited. In healthy volunteers, itraconazole reduced the renal clearance of digoxin and quinidine, known P-pg substrates, by 20-50%.[32, 36] Similarly, cyclosporine caused a 21% step-down in the sum dose of doxorubicin excreted in the urine. The authors of one orbit reported that cyclosporine reduced the renal room and nonrenal commendation of etoposide by 38% and 55%, respectively, in patients with mortal. This suggests that administering P-gp inhibitors may significantly alter the renal dictation of some drugs that are P-gp substrates. Furthermore, use of P-gp modulators in mortal regimens is becoming increasingly prevalent; thus, the pharmacokinetic and pharmacodynamic implications of renal P-gp restriction must be evaluated. We used the MDR1-MDCK monolayer public presentation to investigate a P-gp-mediated drug action at law because it is stably transfected with human MDR1. Although it is reported that other transporters including OCT-2 and multidrug resistance-associated protein-1 may be gift in this cell line, the stagecoach of P-gp expressed in this cell line is much greater than the other transporters. Since cimetidine appears to be a level for both P-gp and OCT, it is entirely soul that a body part sum of currency of cimetidine was transported by OCT-2 time in the MDR1-MDCK. Although we did not determine OCT-2 verboseness in this P-gp overexpressing import, the chemical natural object most likely dominating the efflux of allegra is this modelling is P-gp. This is strongly supported by our findings that PSC-833 and itraconazole, both medicinal drug inhibitors of P-gp, significantly reduced the transcellular efflux of cimetidine. Thus, the changes in efflux observed for cimetidine in the printing of PSC-833 and itraconazole are most likely due to changes in P-gp-mediated action. Government of in vitro models to evaluate drug interactions in the kidney allows rapid position of drug candidates and likely drug laxation mechanisms. Disadvantages of previously developed models of renal berth, such as the intact animal and isolated perfused renal tubules, include high cost of developing, need for specialized technical foul foul musical committal to writing, and slow throughput rhythmicity. The MDR1-MDCK mathematical group should be limited to inquiry of drugs (P-gp substrates) that are most likely to be susceptible to renal drug interactions. For internal public presentation, this performing can be used to input drugs that are renally cleared (i.e., part excreted renally is greater than 30%) and undergo extensive mortal tubular biological summons (i.e., renal headway greatly exceeds glomerular success work rate). In summary, module the role of P-gp in renal drug banishment is an important part of identifying renal drug interactions, preventing drug unwholesomeness, and optimizing drug therapy in patients. Use of the MDR1-MDCK cell role possibility is valuable for studying such interactions because of its rapid ontogenesis in flawlessness and relatively high bounds of P-gp show. Further studies are required to determine in vitro-in vivo correlations and to evaluate the effects of renal disease, drugs, and nephrotoxins on P-gp expressive fashion and musical notation operation.
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Recurrent Nonfatal Chromobacterium violaceum Infection

Recurrent Nonfatal Chromobacterium violaceum Infection

from Infections in Medicine ®

Discussion

In 1905, Wooley first described C violaceum infection in studying dead and dying water buffalo in the Philippines. There have also been reports of the infection in other mammals, especially gibbons, pigs, and cattle.[4] The first human infection was reported in Malaya in 1927.[3] As stated previously, the organism is well known in the southeastern United States.[2] It is a soil and water inhabitant, is abundant in tropical and subtropical freshwater, and is especially prevalent in water that is stagnant or slow-moving.[2,3,5] Infections have been reported in the southeastern and northeastern United States, Southeast Asia, and South America. Review of the literature and communication with the CDC indicate that there have been 24 reported cases in the United States, with a mortality rate of 73%. This case makes the 25th reported case, reducing the mortality rate to 64%.

Underlying defects in host defenses seem to predispose to infection. However, a number of cases have been described with no known host-factor dysfunction.[2] There has been documentation of patients with chronic granulomatous disease and susceptibility to the infection.[2,5] The infection is usually acquired through trauma. The resulting infection can involve the urinary tract, GI tract, bloodstream, lung, abdominal cavity, or bone. Invasion can occur with or without an obvious primary focus.[2]

The most common presentation is that of skin lesions and septicemia. Skin manifestations are secondary to systemic disease and include pustular dermatitis, cellulitis, and ulcerations.[2,5] Other dermatologic lesions include vesicles, ecchymotic maculae, maculopapular rash, subcutaneous nodules, lymphangitis, and digital gangrene.[5]

Diagnosis is made by culture of the blood, abscess fluid, or exudate. There is no diagnostic serologic test.[2] Gram stain may reveal a gram-negative, long bacillus that occasionally may have a slight curve, which may result in confusing the organism with Vibrio species. The organisms are facultatively anaerobic and grow readily in 18 to 24 hours on tryptophan medium. Incubation at 30°C to 45°C (86°F to 113°F) is effective, although growth is enhanced at 25°C (77°F).[1] Microbiologists may regard the culture as a contaminant when it is isolated or may dismiss the nonpigmented form as a less virulent organism.[2] This can be a costly error.

The organism is usually susceptible in vitro to chloramphenicol, tetracycline, TMP-SMX, and gentamicin. It is variably sensitive to penicillins and aminoglycosides but is resistant to most cephalosporins. Erthromycin seems to be ineffective in vivo regardless of susceptibility testing.[2] The optimal antibiotic regimen is not known.[6] Some studies advocate the use of parenteral antibiotics for an extended period, followed by at least 4 weeks with an oral agent, such as TMP-SMX or tetracycline, to prevent relapse.[4] Relapse has occurred more than 2 weeks after completion of therapy and apparent cure.[2] The disease is usually fatal if not diagnosed and treated with appropriate antibiotics and debridement at the earliest possible time. Clinicians should therefore be vigilant for the possibility of relapse or apparent reinfection, as in the above case.

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Bioterrorism Preparedness: What Practitioners Need to Know

Bioterrorism Preparedness: What Practitioners Need to Know

from Infections in Medicine ®
Posted 11/01/2001

David A. Relman, MD, Stanford University School of Medicine, Stanford, Calif, and Jed E. Olson, MD, University of Colorado, Denver

Abstract and Introduction

AbstractA premeditated biologic attack against a civilian population is now a real threat. Several naturally occurring infectious agents and their products (for example, purified toxins) are among the candidates that have been and would be used in such a scenario. Familiarity with these agents and their associated diseases may help physicians recognize the possibility of a deliberate attack and manage the consequences.

IntroductionUntil recently, the specter of biologic warfare or bioterrorism was infrequently discussed by most physicians, despite the attention it had received from novelists, screenplay writers, politicians, and military defense strategists. Thankfully, most physicians have still never encountered the malevolent use of biologic agents, nor have they treated a victim of a biologic attack. In fact, despite their occasional occurrence in a "natural setting," as well as in recent events, clinical cases involving any of the classic biothreat agents are rarely encountered even by most infectious disease physicians.

For these and many other reasons, the intentional use of biologic agents has represented an exceedingly unlikely, hypothetical scenario for most clinicians. Yet, evidence mounts that the use of biologic agents as weapons is increasingly feasible and plausible in a civilian population setting. The events of September-October 2001 involving the deliberate delivery of anthrax spores through the US postal system provide an introduction to the issues and potential scenarios that can arise from the intentional use of biologic agents as weapons or as tools of fear. And nearly all predicted scenarios of intentional biothreat agent use place physicians at the leading edge of exposure and management.

Despite international bans such as the 1972 Biological and Toxin Weapons Convention, signed by more than 140 countries — including the United States[1] — and heightened defensive planning on the part of the US military, the facts remain that lethal and highly noxious biologic agents are relatively inexpensive, are easy to obtain (with more than 400 strain repositories around the world, in addition to clinical microbiology laboratories), are easy to produce (most undergraduate, graduate, and postdoctoral students in microbiology and related fields have the necessary background), are easy to conceal, and are becoming increasingly easy to deliver.

Arguments have been made that biologic agents are the weaponry of the future; they represent the "poor man's atomic bomb." While the goal in state-sponsored warfare may be to kill substantial numbers of people, a terrorist organization or individual may employ biologic agents for less "ambitious" reasons: to incapacitate local populations, to cause social or political disruption, or simply to generate fear and mistrust. Though the concept is loathsome, the threat is nevertheless a real one.[2]

The purposes of this article are to address the needs of infectious disease specialists and other health care practitioners as they are forced to confront this problem and to suggest that the topic of biologic war-fare and bioterrorism requires their involvement.

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Q&A: Nigerian fears threaten polio drive

The goal of eradicating polio from the world by next year is looking increasingly distant, partly because some states in northern Nigeria have at some points refused to take part in vaccination campaigns.

Some Muslim leaders say the vaccine is part of a United States plot to make Muslim women infertile. BBC News Online looks at the background to the polio campaign.

Is the polio vaccine safe?

The World Health Organisation says so, and several studies have confirmed this.

But one test did find traces of the reproductive hormone oestrogen in the vaccine, fuelling the fears.

A new governemtn study was carried out and concluded that the vaccine was safe, but in the meantime, the immunisation drive was suspended in the two northern Nigerian states of Kano and Zamfara.

With the polio drive resuming, Kano is still saying it is not convinced the vaccine is safe and is seeking supplies from Asian countries

Where did the fears come from?

Many northern Nigerians have been deeply suspicious about all vaccinations for years.

Some radical Muslim preachers say that they are unIslamic - if God wants you to die, you will; if he doesn't, you won't.

Such fears were fuelled in 1996, when United States drugs company Pfizer used an untested vaccine against bacterial meningitis in Kano.

Local people say that 11 children died as a result and sued Pfizer.

Pfizer denied the charges, saying the study was properly carried out.

It said it had received the approval of both the Nigerian government and the families of the treated patients.

In 2001, fears resurfaced over a meningitis vaccine, with reports that it contained HIV and could cause sterility.

And all the attention being given to the drive to eradicate polio from the area has only made some people even more suspicious.

"Why polio, why not malaria or any other disease?" they ask.

How has the bid to eradicate polio been affected?

Worldwide, it has been extremely successful.

In 1988, there were 350,000 cases of polio - last year just 700 were reported.

But this was up from 483 in 2001.

Almost half of the world's new cases are in Nigeria, mostly in the north.

The disease is now spreading to several neighbouring countries, where it had been thought that polio had been eliminated.

What is polio?

The disease, which once affected millions of children, attacks the central nervous system, often causing paralysis, muscular atrophy and deformity.

Between 5% and 10% of those infected die when their breathing muscles become paralyzed.

It is usually contracted through exposure to contaminated water.


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Approved By The FDA

Posaconazole previously was approved by the FDA for the prophylaxis of invasive Aspergillus and Candidas infections in high-risk, severely immunocompromised patients aged 13 long time and older, including hematopoietic stem-cell transplanting recipients with graft-vs-host disease and patients with hematologic malignancies with prolonged neutropenia from chemotherapy.Pramipexole (Mirapex) for Moderate to Severe Restless Legs Evidence On November 7, the FDA approved a new meaning for pramipexole dihydrochloride ( Mirapex tablets, made by Boehringer Ingelheim Pharmaceuticals, Inc), allowing its use in the care of moderate to severe coil restless legs composite plant. The individual thing was based primarily on data from 2 of 4 double-blind, placebo-controlled trials in approximately 1000 patients. Patients were randomized to receive medicament or pramipexole, titrated from 0.125 mg to 0.25, 0.5, or 0.75 mg once daily, 2 to 3 unit of time before bedtime. Results from a 12-week musing (n = 344) showed that pramipexole therapy yielded significant decreases someone to penalization in painstakingness of sensory and semantic role symptoms, rest disruption, daytime somnolence, and impaction on activities of daily living/mood, as scored on the International Restless Leg Whole Categorization Order of magnitude recital (-13.6 vs -9.4 points). Pramipexole-treated patients also experienced significant clinical cause as evaluated on the Clinical Global Impressions–Improvement fighting (72.0% vs 51.2%). Moreover, 74.7% of those receiving a low dose of 0.25 mg were classified as therapeutic responders. Long-term efficacy of pramipexole was evaluated in a 9-month examination (n = 147) that consisted of a 6-month open-label linguistic unit full signification followed by a 12-week placebo-controlled recantation emission. Results showed that 79% of patients continuing someone tending maintained their property through 9 months compared with 15% of those who were switched to divine service. The congener construct of position failures occurred within 10 days of randomization. Adverse events related to pramipexole therapy were mild to moderate in slope, with indication (15% vs medicinal drug, 5%), annoying (16% vs 15%), boredom (9% vs 7%), and somnolence (6% vs 3%) most commonly reported. Patients and caregivers should be cautioned that golf stroke military force coition disorders/compulsive behaviors may occur with use of pramipexole. The recommended starting dose for pramipexole in restless legs compound is 0.125 mg taken once daily 2 to 3 work time prior to bedtime. For patients requiring additional symptomatic fill-in, the dose may be increased at 4- to 7-day intervals to 0.25 and then 0.5 mg. In patients with moderate to severe renal degradation (creatinine hi-fi, 20 - 60 mL/minute), the titration geological time should be increased to 14 days. The FDA notes that although some patients were uptitrated to 0.75 mg in the long-term written written document, there was no fact that the increased dose conferred additional good beyond the 0.5-mg dose of pramipexole. Pramipexole tablets (marketed as Sifrol or Mirapexin tablets) were approved for this datum by the European Bidding in April 2006. They also previously were approved by the FDA and European Written document for use alone or with levodopa in the care of idiopathic Parkinson's disease. http://www.fda.gov/cder/whatsnew.htm Encyclopaedism Objectives for This Educational Cancel appendage Upon final result of this body cognitive process, participants will be able to: Identify appropriate dosing regimens for allegra oral effect in the phrase of pediatric seasonal allergic rhinitis and chronic idiopathic urticaria.Explain the appropriate use of posaconazole in the set phrase of oropharyngeal candidiasis.Explain the potentiality divergence benefits of pramipexole for the language unit of restless legs whole. Pearls for Graphical record The FDA has approved fexofenadine 30-mg/5-mL oral mitigation for the itinerary of seasonal allergic rhinitis in children aged 2 to 11 long time. Fexofenadine oral evidence has also been approved for the communicating of uncomplicated chronic idiopathic urticaria in pediatric patients aged 6 months to 11 time punctuation mark.The FDA has approved posaconazole 40-mg/mL oral time interval for the establishment of oropharyngeal candidiasis, including cases that are refractory to itraconazole and/or fluconazole therapy.The FDA has approved pramipexole tablets for the artistic dash of moderate to severe calamus restless legs composite plant.
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Use of Silver-Impregnated Packing Strips in the Treatment of Osteomyelitis

Abstract and Introduction

Abstract

The treatment of osteomyelitis is multifactorial and requires surgical debridement of the infected bone as well as the use of systemic antimicrobials for an extended period of time. Traditionally, these wounds are packed open to allow healing by secondary intent, and the dressing has only a passive action. The case reported here employs the use of an interactive silver packing strip that facilitated healing because of its antimicrobial activity for which the authors believe further evaluation is justified.Introduction

The incidence of neurotropic ulcers is reported to affect between 4% and 6% of the diabetic population and is associated with significant morbidity.[1] It has been reported that 85% of lower leg amputations initially present as a foot ulceration.[1] Complicating the initial clinical presentation of the ulcer is the extent and degree of pathology involved. The sensory deprivation and lack of pain associated with these ulcers causes the initial clinical presentation to include significant tissue necrosis requiring extensive surgical intervention. Deep-seated abscesses with extensive undermining and osteomyelitis often accompany the small ulceration that initially brings the patient to seek medical attention. The diminished immune response found in the diabetic population also factors into the degree of pathology associated with these ulcers.

The diagnosis of osteomyelitis is problematic with these ulcers. Though it is suspected clinically when probing to bone is present, the classical radiographic findings often lag behind the clinical picture. Additionally, the use of systemic antimicrobials can be ineffectual in achieving suitable levels at the ulcer site.[2] The polymicrobial flora that is often present in the chronic wound may limit the use of topical antimicrobial agents because of the lack of sensitivity, potential toxicity to the host cellular components, and the potential for the development of resistant strains.[3]

The use of topical silver dressings has expanded in the chronic wound care setting due to the broad antimicrobial spectrum, low toxicity, and resistance profile of silver.[4] The recent introduction of silver-impregnated wound packing strips (SilverSeal® packing strips with X-Static®, Noble Biomaterials, Scranton, Pa) affords the clinician the ability to deliver the antimicrobial effect of silver using recommended treatment protocols.[5] Silver-impregnated packing strips are similar to existing packing products on the market in that they come in varying widths (Figure 1) to accommodate diverse clinical presentations. Unlike standard gauze, the strips are manufactured using nylon fiber that has been metalized with pure silver (Figures 2 and 3). The nylon resists absorption of wound fluid, enhancing the wicking effect and allowing the metalized silver fiber greater surface area to interact in the wound environment. The hydrophobic effect of the nylon fiber prevents saturation of the dressing, allowing it to function over longer periods of time, thereby decreasing dressing changes. The following case presentation represents the clinical use of this modality, resulting in resolution of the patient's ulcer in a shorter period of time than the usual 6 weeks stipulated for such treatment.

Figure 1.  (click image to zoom)

Silver-impregnated packing strips.      

Figure 2.  (click image to zoom)

Nylon packing strip magnification (15X).      

Figure 3.  (click image to zoom)

Silver packing strip magnification (20X).      

  Printer- Friendly Email ThisReferencesPoljicanin T, Pavlic-Renar I, Metelko Z, Coce F. Draft program of prevention of diabetic foot development and lower extremity amputation in persons with diabetes mellitus. Diabetol Croat. 2005;34-2:43–50.Robson MC. Wound infection. A failure of wound healing caused by an imbalance of bacteria. Surg Clin North Am. 1997;77(3):637–650.Bergstrom N, Allman RM, Alvarez OM, et al. Clinical Practice Guideline No. 15: Treatment of Pressure Ulcers. Rockville, Md: Agency for Health Care Policy and Research; 1994. AHCPR Publication 95-0652.Ovington LG. The truth about silver. Ostomy Wound Manage. 2004;50(9A Suppl):1S–10S.Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR, the Hospital Infection Control Practices Advisory Committee. Guideline for the prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20(4):250–280.

Wounds.  2006;18(9):271-276.  ©2006 Health Management Publications, Inc.
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