David B. Huang

Thalidomide: dermatological indications, mechanisms of action and side-effects.

Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration‐approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçets syndrome, graft‐versus‐host disease, cutaneous sarcoidosis, erythema multiforme, Jessner–Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.

Problem pathogens: extra-intestinal complications of Salmonella enterica serotype Typhi infection

Typhoid fever, caused by Salmonella enterica seroptype Typhi (S typhi), has an estimated worldwide prevalence of 12-33 million cases. The pathogenesis of this disease depends on the ingested inoculum size of S typhi, the virulence of the strain, the hosts immune response and previous exposure, and local protective factors. Numerous extra-intestinal complications can occur with S typhi infection, including the involvement of the central nervous system (3-35%), cardiovascular system (1-5%), pulmonary system (1-86%), bone and joints (< or =1%), hepatobiliary system (1-26%), genitourinary system (<1%), and others. Due to an increase in multidrug-resistant S typhi, fluoroquinolones and third-generation cephalosporins have been increasingly used for typhoid fever and its complications. We describe the epidemiology, clinical manifestations, pathogenesis, and treatment of extra-intestinal S typhi infections.

Lysins: the arrival of pathogen-directed anti-infectives

Lysins represent a novel class of anti-infectives derived from bacteriophage. Lysins are bacterial cell-wall hydrolytic enzymes that selectively and rapidly kill (≥3 log c.f.u. in 30 min) specific Gram-positive bacteria providing a targeted therapeutic approach with minimal impact on unrelated commensal flora. The potential for bacterial resistance to lysins is considered low due to targeting of highly conserved peptidoglycan components. Through cutting-edge genetic engineering, lysins can be assembled into large libraries of anti-infective agents tailored to any bacterium of interest including drug-resistant Gram-positive pathogens such as meticillin- and vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, and penicillin-resistant Streptococcus pneumoniae. Lysins can eliminate bacteria systemically and topically from mucosal surfaces and biofilms, as evidenced by experimental models of sepsis, endocarditis, pneumonia, meningitis, and nasopharyngeal, skin and vaginal decolonization. Furthermore, lysins can act synergistically with antibiotics and, in the process, resensitize bacteria to non-susceptible antibiotics. Clinical trials are being prepared to assess the safety and pharmacokinetic properties of lysins in humans.

Enteroaggregative Escherichia coli Is a Cause of Acute Diarrheal Illness: A Meta-Analysis

BACKGROUND Conflicting studies exist regarding the role of enteroaggregative Escherichia coli (EAEC) as a cause of acute diarrheal illness. The objective of this meta-analysis was to determine whether identification of EAEC in stool samples is associated with acute diarrheal illness among different subpopulations, by geographic area. METHODS A comprehensive search of electronic bibliographic databases (Medline and PubMed) from August 1985 to January 2006, as well as a search of conference proceedings, references of articles, and contacts with investigators of EAEC, yielded 354 studies. RESULTS Forty-one studies (12%) that met the selection criteria (i.e., that examined the association between acute diarrheal illness and the excretion of EAEC among different subpopulations) were included. In this meta-analysis, presence of EAEC identified with the HEp-2 cell adherence assay was found to be significantly associated with acute diarrheal illness among children residing in developing regions (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36-1.83) and industrialized regions (OR, 1.23; 95% CI, 1.03-1.48), adults with human immunodeficiency virus infection residing in developing regions (OR, 6.43; 95% CI, 2.91-14.16), adults residing in developing regions (OR, 7.15; 95% CI, 1.96-26.04), and international travelers to developing regions (OR, 6.72; 95% CI, 2.62-17.20). A limited number of studies were available that examined the role of EAEC identified by its virulence genes by a DNA probe. CONCLUSIONS On the basis of this meta-analysis, we conclude that EAEC is a cause of acute diarrheal illness among many different subpopulations in both developing and industrialized regions, that EAEC strains are very heterogeneous and that additional studies that examine the role of EAEC in acute diarrheal illness are needed.

Enteroaggregative Escherichia coli: An Emerging Enteric Pathogen

Enteroaggregative Escherichiacoli (EAEC) represents an emerging pathogen that causes enteric and food-borne infectious diseases. Subgroups in many populations throughout the world are susceptible to EAEC infection. EAEC pathogenesis involves adherence to the intestinal mucosa; increased production and deposition of a mucus biofilm; and mucosal toxicity due to inflammation and cytokine release. Due to the heterogeneity of EAEC strains and differing host immune responses, not all EAEC infections are symptomatic. Recent data suggest that individuals with a homozygous genotype –251 AA single nucleotide polymorphism (SNP), in the IL-8 promoter region, are more susceptible to EAEC diarrhea. The HEp-2 cell adherent assay allows identification of EAECs characteristic aggregative or “stacked brick” adherence pattern. Antimicrobial treatment of individuals who develop EAEC diarrhea should be individually based. Ciprofloxacin and rifaximin, compared to placebo, have been shown to significantly shorten the course of diarrhea in patients who developed EAEC infection. The objective of this review is to increase awareness of this important emerging pathogen and to discuss the epidemiology, pathogenesis, and host-pathogen factors associated with EAEC infection.

Subcutaneous fungal infections

ABSTRACT:  Subcutaneous mycoses are caused by a variety of mostly tropical organisms, usually when they are implanted into the dermis or the subcutaneous tissue. They rarely disseminate or become systemic. Sporotrichosis, mycetoma, and chromoblastomycosis are more common subcutaneous mycoses than are rhinosporidiosis, zygomycosis, pheohyphomycosis, and lobomycosis.

Combination Therapy With Lysin CF-301 and Antibiotic Is Superior to Antibiotic Alone for Treating Methicillin-Resistant Staphylococcus aureus–Induced Murine Bacteremia

Lysins are bacteriophage-derived enzymes that degrade bacterial peptidoglycans. Lysin CF-301 is being developed to treat Staphylococcus aureus because of its potent, specific, and rapid bacteriolytic effects. It also demonstrates activity on drug-resistant strains, has a low resistance profile, eradicates biofilms, and acts synergistically with antibiotics. CF-301 was bacteriolytic against 250 S. aureus strains tested including 120 methicillin-resistant S. aureus (MRSA) isolates. In time-kill studies with 62 strains, CF-301 reduced S. aureus by 3-log10 within 30 minutes compared to 6–12 hours required by antibiotics. In bacteremia, CF-301 increased survival by reducing blood MRSA 100-fold within 1 hour. Combinations of CF-301 with vancomycin or daptomycin synergized in vitro and increased survival significantly in staphylococcal-induced bacteremia compared to treatment with antibiotics alone (P < .0001). Superiority of CF-301 combinations with antibiotics was confirmed in 26 independent bacteremia studies. Combinations including CF-301 and antibiotics represent an attractive alternative to antibiotic monotherapies currently used to treat S. aureus bacteremia.

Association of Putative Enteroaggregative Escherichia coli Virulence Genes and Biofilm Production in Isolates from Travelers to Developing Countries

ABSTRACT Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen that causes acute and chronic diarrhea among children, human immunodeficiency virus-infected patients, and travelers to developing regions of the world. The pathogenesis of EAEC strains involves the production of biofilm. In this study, we determined the association between presence of putative EAEC virulence genes and biofilm formation in 57 EAEC isolates (as defined by HEp-2 adherence) from travelers with diarrhea and in 18 EAEC isolates from travelers without diarrhea. Twelve nondiarrheagenic E. coli isolates from healthy travelers were used as controls. Biofilm formation was measured by using a microtiter plate assay with the crystal violet staining method, and the presence of the putative EAEC virulence genes aap, aatA, aggR, astA, irp2, pet, set1A, and shf was determined by PCR. EAEC isolates were more likely to produce biofilm than nondiarrheagenic E. coli isolates (P = 0.027), and the production of biofilm was associated with the virulence genes aggR, set1A, aatA, and irp2, which were found in 16 (40%), 17 (43%), 10 (25%), and 27 (68%) of the biofilm producers versus only 4 (11%), 6 (6%), 2 (6%), and 15 (43%) in non-biofilm producers (P = 0.008 for aggR, P = 0.0004 for set1A, P = 0.029 for aatA, and P = 0.04 for irp2). Although the proportion of EAEC isolates producing biofilm in patients with diarrhea (51%) was similar to that in patients without diarrhea (61%), biofilm production was related to the carriage of aggR (P = 0.015), set1A (P = 0.001), and aatA (P = 0.025). Since aggR is a master regulator of EAEC, the presence of aap (P = 0.004), astA (P = 0.001), irp2 (P = 0.0006), pet (P = 0.002), and set1A (P = 0.014) in an aggR versus an aggR-lacking background was investigated and was also found to be associated with biofilm production. This study suggests that biofilm formation is a common phenomenon among EAEC isolates derived from travelers with or without diarrhea and that multiple genes associated with biofilm formation are regulated by aggR.

Laboratory measurement of aggression in high school age athletes: provocation in a nonsporting context.

This study investigated the relationship between aggression and type of sports involvement in high school age boys. Athletes (16 boys), ages 15 to 18 years, were separated into two groups, one of 8 athletes who participated in sports with high physical contact, e.g., football and basketball, and the other of 8 athletes who participated in low contact sports, e.g., track and baseball. Students participated in six 25-min. Point Subtraction Aggression Paradigm sessions. The paradigm is an established laboratory model of aggression with three response options: (1) a point-maintained response, (2) an aggressive response, and (3) an escape response. Analysis indicated that the only difference between the groups was that individuals who participated in high contact sports emitted significantly more aggressive responses than individuals who participated in low contact sports. Similarly, psychometric measures of aggression indicated that individuals in the former group self-reported more behavioral incidents of aggression than those in the latter group.

A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines

Abstract Viral vaccines could be considered among the most important medical achievements of the 20th century. They have prevented much suffering and saved many lives. Although some curative antiviral drugs exist, we desperately depend on efforts by academic, governmental and industrial scientists in the advancement of viral vaccines in the prevention and control of infectious diseases. In the next decade, we hope to see advancement in the development of current and investigational viral vaccines against childhood and adult infections. In this article, we will review the licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines.