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.

This is a part of article Recurrent Nonfatal Chromobacterium violaceum Infection Taken from "Chloromycetin Chloramphenicol 250Mg" Information Blog

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.

This is a part of article Bioterrorism Preparedness: What Practitioners Need to Know Taken from "Chloromycetin Chloramphenicol 250Mg" Information Blog

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.

This is a part of article Q&A: Nigerian fears threaten polio drive Taken from "Chloromycetin Chloramphenicol 250Mg" Information Blog

Tomoo Kuge, Ph.D.; Takashi Shibata, M.D., Ph.D.; Michael S. Willett, Pharm.D.

Abstract and Introduction

Abstract

Study Objective: To assess the safety, tolerability, and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent.
Design: Randomized, double-blind, placebo-controlled study.
Setting: Clinical research center.
Subjects: Forty (32 men, 8 women) healthy volunteers aged 19-42 years.
Intervention: By random assignment, 22 men and 8 women received escalating single doses of wood creosote (45, 90, 135, 180, and 225 mg) and 10 men received placebo (for each of the five dose levels, 6 subjects received active substance and 2 subjects received placebo).
Measurements and Main Results: Vital signs, laboratory tests, and electrocardiograms were assessed; no dose-related or clinically significant changes were noted. Serial blood samples were obtained to determine the pharmacokinetics of four major active components of wood creosote: total (conjugated plus free) guaiacol, creosol, o-cresol, and 4-ethylguaiacol. The most common adverse events were mild headache and dizziness, with no dose-related trends being apparent. Area under the concentration-time curve from time zero to infinity increased in a dose-proportional manner for total guaiacol, creosol, and o-cresol and was not assessed for total 4-ethylguaiacol owing to lack of data at the low dose level. No apparent differences by sex were noted for any of the four active components. All four components were rapidly eliminated.
Conclusion: Single oral doses of wood creosote up to 225 mg were safe and well tolerated in healthy men and women. Also, the doses of wood creosote were rapidly absorbed, conjugated, and eliminated. Such a rapid onset and short duration of action would appear desirable in the treatment of acute nonspecific diarrhea.Introduction

Diarrhea is recognized as a major health problem and one of the leading causes of infant mortality in developing countries.[1-3] Diarrheal illness is also common in developed countries but usually is viewed as an inconvenience rather than a medical hazard. In developed countries, most episodes of diarrhea are mild and are either self-limiting or self-treated with over-the-counter drugs or home remedies. Nonetheless, acute diarrhea significantly affects the United States population through restriction in activity and loss in productivity.[4] In addition, there are certain high-risk populations (e.g., infants, elderly patients with concomitant medical conditions, immunocompromised patients) for whom diarrhea can be severely debilitating. Traveler's diarrhea, although often self-limiting, can also be severe. In some developing countries, the frequency of traveler's diarrhea can exceed 50%.[5, 6]

The cause of acute diarrhea in the United States most often is thought to be infectious; however, in clinical practice, a pathogen is identified less than 50% of the time. Diarrhea in infants and children in the United States is usually associated with infections caused by rotavirus. In adults in the United States, the causative agent may be a bacterial or viral pathogen or may be noninfectious. In clinical trials, traveler's diarrhea is caused by bacterial pathogens in more than half of the cases.[7]

Diarrhea, having many different causes and therefore different effects on the gastrointestinal system, can be categorized based on potential mechanisms of altered fluid and electrolyte movement.[8] The pathophysiologic manifestations of acute diarrhea often include increased luminal osmolality, increased intestinal secretion, inflammation of the intestinal lining, and altered intestinal motility. The goal in management is to correct the underlying pathophysiologic problem when feasible and to provide symptomatic relief.

Available treatments, including prescription and over-the-counter drugs, have several disadvantages. Antibiotic treatment is generally not recommended for most cases of mild-to-moderate, acute, nonspecific diarrhea because the risks of overuse may outweigh the benefits. Other drugs used to treat diarrhea, such as those containing diphenoxylate hydrochloride and atropine, can have central nervous system adverse effects and may be contraindicated in some patients.[9] Loperamide, the most commonly administered drug to treat acute diarrhea, is safe and effective, but it can cause other gastrointestinal adverse effects, such as constipation and abdominal cramps.[10]

Wood creosote is an herbal medicine that has been used as an antidiarrheal and antispasmodic agent in Japan and in other countries in the Pacific Rim under the brand name Seirogan (currently marketed by Taiko Pharmaceutical Company, Ltd., Osaka, Japan) for the past century. Wood creosote also has been used for medicinal purposes in Europe since the early 1800s.[11] Approximately 1.16 billion Seirogan tablets (wood creosote 45 mg/tablet) are sold worldwide each year, representing approximately 42.8 million patient treatment courses, estimated based on a 3-day treatment course of three tablets/dose taken 3 times/day (27 tablets/course). Seirogan recently has been marketed in the United States as an over-the-counter herbal product and is approved in Canada as an over-the-counter drug (drug identification number 02243423). Total Seirogan sales in North America account for less than 5% of worldwide sales at the present time. Seirogan typically is taken for up to 3 days as an acute antidiarrheal agent, and patients typically report relief of symptoms after one to two doses. There are no known drug-drug interactions or contraindications with Seirogan.

Wood creosote (CAS-8021-39-4), also referred to as medicinal creosote, is a mixture of simple phenolic compounds, including guaiacol, creosol, o-cresol, and 4-ethylguaiacol as major active components,[12] and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. A long-term safety study in rats documented a lack of oncogenicity for wood creosote.[13]

Wood creosote has been shown to suppress gastrointestinal motility, with a consequent increase in intestinal transit time and increase in net fluid absorption from the intestine in in vivo and ex vivo animal models.[14-16] Clinical experience in humans indicates that wood creosote relieves acute diarrhea, often within one or two doses; suppresses intestinal hypermotility; and produces an antispasmodic effect in the setting of acute diarrhea. Also, decreased stool volume and frequency have been observed by clinicians in anecdotal reports.

Despite many years of postmarketing experience with Seirogan, in Asia in particular, rigorously controlled clinical studies evaluating the safety and efficacy of wood creosote are lacking. The objective of our study was to assess the safety, tolerability, and pharmacokinetics of escalating single doses of wood creosote in a rigorous manner with a double-blind, placebo-controlled study design. The Seirogan tablet formulation marketed worldwide contains wood creosote plus other herbal ingredients, including gambir, philodendron bark, glycyrrhiza, and citrus unshiu peel. The formulation evaluated in this study is a sugar-coated tablet that contains wood creosote 45 mg as the principal active ingredient without the other herbal components.

Section 1 of 5 Tomoo Kuge, Ph.D., Takashi Shibata, M.D., Ph.D., and Michael S. Willett, Pharm.D.

From Taiko Pharmaceutical Company, Ltd., Osaka, Japan (Drs. Kuge and Shibata); the Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan (Dr. Kuge); and Advanced Biomedical Research, Inc., Pennington, New Jersey (Dr. Willett).
Pharmacotherapy 23(11):1391-1400, 2003. © 2003 Pharmacotherapy Publications
This is a part of article Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medicine: A Single-Dose, Dose-Escalation Safety and Pharmacokinetic Study Taken from "Atropine Sulfate" Information Blog

Biological Actions of Ghrelin

Ghrelin and Hypothalamus–Pituitary Endocrine Functions

GH-Releasing Activity. Ghrelin, as well as synthetic GHS, possesses a strong and dose-related GH-releasing effect (Kojima et al., 1999; Arvat et al., 2000, 2001; Peino et al., 2000; Seoane et al., 2000; Takaya et al., 2000; Wren et al., 2000; Broglio et al., 2003a). Ghrelin and GHRH have a synergistic effect indicating that they act, at least partially, via different mechanisms (Arvat et al., 2001; Hataya et al., 2001; Cunha & Mayo, 2002). Nevertheless, GH secretagogues need GHRH activity to fully elicit their GH-releasing effect and probably act by triggering GHRH-secreting neurones, being strongly inhibited by a GHRH antagonist as well as by a hypothalamus–pituitary disconnection (Pandya et al., 1998; Tannenbaum & Bowers, 2001; Popovic et al., 2003; Tannenbaum et al., 2003; Kamegai et al., 2004).

Ghrelin probably also acts as a functional somatostatin antagonist at both the pituitary and the hypothalamic level (Tannenbaum et al., 2003). In humans the GH response to ghrelin is partially refractory to exogenous somatostatin or cortistatin (Broglio et al., 2002a; Di Vito et al., 2002). The GH response to ghrelin and GHS is also partially refractory to other factors known to affect somatotroph secretion, such as glucose, lipids, arginine, cholinergic agonists and antagonists, IGF-I and GH itself (Broglio et al., 2002b,c; van der Lely et al., 2004). The GH-releasing action of ghrelin and GHS undergoes homologous desensitization under prolonged exposure to these molecules in both animals and humans (Micic et al., 2002; Orkin et al., 2003; Camina et al., 2004).

The GH-releasing effect of ghrelin and GHS is influenced by pharmacological doses of oestrogens; however, the somatotroph response to ghrelin administration is independent of gender while it undergoes marked age-related variations (Broglio et al., 2003a; van der Lely et al., 2004). As a reduced expression of the hypothalamic GHS receptors has been demonstrated in the aged human brain, an impairment of the ghrelin system could theoretically have a role in the age-related decrease of GH secretion (Muccioli et al., 1998; van der Lely et al., 2004).

Interestingly, the GH response to ghrelin has been reported to be clearly reduced not only in obesity, where it was expected due to the functional hyposomatotropism commonly present in this condition, but also in anorexia nervosa, a condition in which both spontaneous and GHRH-stimulated GH secretion have been reported to be increased (Tassone et al., 2003; Broglio et al., 2004a; varez-Castro et al., 2004). These findings suggest that in anorexia nervosa, chronic hyperghrelinaemia could induce some desensitization to exogenous ghrelin actions.

Ghrelin is likely to play a role in the GH response to fasting and energy restriction; the GH hyper- and hyposecretion that connote anorexia and obesity, respectively, could reflect the ghrelin hyper- and hyposecretion that have been demonstrated in these clinical conditions (Ariyasu et al., 2001; Tschop et al., 2001b; Shiiya et al., 2002). However, a feedback link between GH and ghrelin secretion has never been demonstrated and ghrelin does not play a role in mediating the GH response to the majority of pharmacological stimuli of somatotroph secretion such as insulin-induced hypoglycaemia, arginine, glucagon and cholinergic agonists (Lucidi et al., 2002; Broglio et al., 2004c,d).

PRL- and ACTH-releasing Activity. The stimulatory effect of ghrelin and GHS on PRL secretion in humans is slight, independent of both gender and age and probably involving both direct action on somatomammotroph cells and indirect hypothalamic actions (Arvat et al., 2001; Broglio et al., 2003a; Korbonits et al., 2004).

The acute stimulatory effect of ghrelin and GHS on the activity of the hypothalamic–pituitary (HPA) axis in humans is similar to that after naloxone, AVP and even corticotrophin-releasing hormone (CRH) but prolonged GHS administration apparently does not lead to an HPA axis hyperfunction (Korbonits et al., 2004; van der Lely et al., 2004). In physiological conditions, the ACTH-releasing activity of GHS depends totally on CNS-mediated mechanisms and probably involves CRH, AVP, neuropeptide Y (NPY) and Gamma-Aminobutyric Acid (GABA) neurones (Korbonits et al., 2004; van der Lely et al., 2004).

The ACTH response to GHS is generally sensitive to the negative feedback control by cortisol (van der Lely et al., 2004). However, the stimulatory effect of ghrelin and GHS on corticotroph secretion is surprisingly enhanced and higher than that of hCRH in patients with pituitary ACTH-dependent Cushing's disease, probably reflecting an action on the pituitary tumoral corticotroph cells where both ghrelin and GHS-R are expressed (Leal-Cerro et al., 2002). Ghrelin and GHS-R expression have also been shown in some ectopic ACTH-releasing tumours and, accordingly, enhanced ACTH and cortisol responses to ghrelin has been reported in some patients with ectopic Cushing's syndrome (Korbonits et al., 2001a, 2004; Leal-Cerro et al., 2002).

Influence on Gonadotroph Secretion. Intracerebroventricular injection of ghrelin has been reported to be able to decrease the frequency of pulsatile LH secretion leading to a decrease in LH concentration (Furuta et al., 2001; Fernandez-Fernandez et al., 2004). These findings probably reflect a modulation of the activity of the GnRH pulse generator and indicate that ghrelin also plays a role in the central control of gonadotroph function (Furuta et al., 2001). Overall, this neuroendocrine action of ghrelin would fit well with the hypothesis that ghrelin, in collaboration with leptin, plays a role in the prompt turn-off of the gonadal axis that, coupled with the amplification of somatotroph and corticotroph functions, occurs during starvation. Ghrelin could, however, also play a role in the control of the gonadal axis at the peripheral level (see below).  Printer- Friendly Email This

Clin Endocrinol.  2005;62(1):1-17.  ©2005 Blackwell Publishing
This is a part of article Ghrelin: More Than a Natural GH Secretagogue Taken from "Atropine Sulfate" Information Blog