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To investigate which subsets of peripheral blood mononuclear cells (PBMCs) are susceptible to infection with hepatitis C virus (HCV) and hepatitis G virus (HGV) or GB virus C (GBV-C), a PCR-based assay using tagged primers in the core region (HCV) and NS3 region (HGV/GBV-C) for the specific detection of negative strand (replicating) viral RNA sequences was developed. In liver biopsy samples both positive and negative strands of HCV RNA were detected, at levels ranging from 3 to 11 x 10(6) RNA copies per 10(6) cells and 3.7-4.2 x 10(3) copies per 10(6) cells respectively, while lower frequencies of positive strands of GBV-C/HGV RNA were detected (from 13 biopsies, the highest frequency was 7.3 x 10(3) per 10(6) cells). In no samples were negative RNA strands detected. To investigate extra-hepatic replication of HCV and GBV-C/HGV, CD4+, CD8+ and B lymphocytes, monocytes and putative dendritic cell populations were separated from PBMCs from ten study subjects. Detection of positive strand HCV RNA was largely confined to B lymphocytes (at levels of up to 5 x 10(3) copies per 10(6) cells), while detection of negative strands was confined to a single subset (dendritic cells) of one of the study individuals. Similarly, GBV-C/HGV was detected at low levels in only twelve of twenty PBMC samples, while negative strands were uniformly absent. The low levels of HCV and GBV-C/HGV RNA in PBMCs suggest that these cells are at most a minor reservoir for virus replication. The absence of detectable replication of GBV-C/HGV suggests that the actual site of GBV-C/HGV replication remains to be discovered.

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BACKGROUND: The clinical significance of a single assessment of circulating hepatitis C virus (HCV) RNA and its relation to the level of intrahepatic HCV RNA remains unclear. AIMS: To investigate the relation between intrahepatic HCV levels and clinicopathological characteristics of chronic HCV infection. PATIENTS: Ninety eight consecutive patients with chronic HCV infection were studied; none had received alpha interferon therapy. Of these, 12 patients were repeatedly negative for HCV RNA in serum by reverse transcriptase polymerase chain reaction (RT-PCR). METHODS: After diagnostic laparoscopy and liver biopsy, semiquantitative analysis of intrahepatic HCV RNA levels was carried out by limiting dilution of HCV cDNA. HCV genotypes were assessed in 96 patients by restriction fragment length polymorphism analysis of HCV cDNA. RESULTS: Ten out of 12 patients who were RT-PCR negative for HCV RNA in serum were RT-PCR positive in liver; however, this group had a significantly lower intrahepatic HCV level and serum aminotransferase level than the remaining 86 patients. Histological severity (cirrhosis: n = 10); histological activity index; HCV genotype (genotype 1: n = 41; genotype 2: n = 12; genotype 3: n = 36; genotype 4: n = 7); mode of infection (intravenous drug abuse: n = 58; post-transfusion: n = 10; haemophiliac: n = 4; sporadic: n = 26) and alcohol abuse did not affect the intrahepatic virus level. There was no correlation between patient age, duration of infection, and intrahepatic HCV level. CONCLUSIONS: Intrahepatic virus levels were not determined by host factors (age of patient, mode or duration of infection) or by virus factors (HCV genotype). Repeatedly negative RT-PCR for HCV RNA in serum does not indicate absence of HCV from the liver.

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infectious disease


Cutaneous fungal infections are superficial infections typically involving the skin, hair, and nails. Most commonly, these fungal infections are caused by dermatophytes, but they can also be caused by nondermatophyte fungi and yeast ( species). The term refers to a fungal organism that causes tinea, a fungal infection. Thus, dermatophytoses are known as , which are further classified by the region of the body infected (e.g., tinea pedis, tinea capitis).

Dermatophytoses are limited to the stratum corneum, nails, and hair shafts because they require keratin for growth. The prevalent dermatophytic infections in the United States include tinea pedis (foot), tinea corporis (body), tinea cruris (groin), tinea capitis (scalp), and tinea unguium (nail). In the U.S., there are three dermatophyte genera that cause infections: , , and . is the most prevalent genus, accounting for approximately 80% of dermatophytic infections in the U.S. The most common mode of transmission of dermatophytes is by direct contact with other people (anthropophilic organisms), but transmission also occurs via contact with animals (zoophilic organisms), the soil (geophilic organisms), and fomites. Individuals most susceptible to fungal skin infections include those who are obese, immunodeficient, or immunosuppressed or have impaired circulation. Fungal infections are also more likely to occur with prolonged exposure to sweaty clothes or bedding, poor hygiene, and residence in warm, humid climates.

The classic appearance of a cutaneous tinea infection is a central clearing surrounded by an active border of redness and scaling, which gives rise to the more common name, . One key point in recognizing a cutaneous fungal infection is the location; tinea infections have no mucosal involvement, since dermatophytes invade only keratinized tissue. Despite having a classic appearance, tinea infections may be similar in appearance to many other dermatologic conditions and are often misdiagnosed and, therefore, mistreated. This article will guide pharmacists to recognize the most common fungal infections, understand the most effective treatment options, and provide counseling for treatment and prevention.

Types of Dermatophytoses

Tinea pedis is the most prevalent cutaneous fungal infection. Frequently referred to as , it affects approximately 26.5 million Americans per year. It is estimated that approximately 70% of people will have tinea pedis during their lifetime.

Four clinically accepted variants of tinea pedis exist; however, they sometimes overlap. The most common variant is intertriginous, which is characterized by fissuring, scaling, or maceration of the interdigital areas; foul odor; itching; and a stinging sensation. The infection often involves the lateral toe webs and may spread to the sole or instep of the foot. Warm, humid conditions may aggravate the area. The second variant is a chronic papulosquamous type that often occurs on both feet. Mild inflammation and dispersed scaling of the skin on the soles of the feet are characteristic of this type. The third variant is composed of small vesicles or vesicopustules on the instep and plantar surface. Scaling of the skin in this area, as well as the toe webs, is observed. The fourth variant involves macerated, denuded, weeping ulcerations on the sole of the foot. Odor is common with this type. This variant is often complicated by opportunistic gram-negative bacteria. Differential diagnosis includes eczema, contact dermatitis, psoriasis, and pitted keratolysis.

Adults typically have an increased risk of tinea pedis compared with children, owing to increased exposure opportunities. Persons who use public pools or bathing facilities are at increased risk. Individuals who participate in high-impact activities that cause chronic trauma to the foot and those who wear occlusive footwear are also at increased risk. Treatment with topical agents is the preferred therapy. Systemic antifungal agents may be required for failed treatment with topical agents, extensive disease, or an immunocompromised state.

Also called , tinea corporis may present in multiple ways and on multiple areas of the body. Lesions frequently manifest as small, circular, erythematous, scaly spaces. Central clearing occurs as the borders spread and vesicles or pustules develop. Tinea corporis may occur on any body part, depending upon the type of dermatophyte infection. Zoophilic dermatophytes frequently infect areas of exposed skin, whereas anthropophilic dermatophytes infect occluded areas or sites of trauma. Differential diagnosis includes eczema, psoriasis, and seborrheic dermatitis.

Tinea cruris, or , occurs on the medial and upper area of the thighs and groin area and is more common in males than in females. The scrotum itself often is not affected. Signs of excessive moisture, pruritus, and burning are often present. Risk factors for tinea cruris include infection with tinea pedis, obesity, diabetes, and immunodeficiency. Differential diagnosis includes candidiasis, intertrigo, erythrasma, psoriasis, and seborrheic dermatitis.

Tinea capitis is also called . The incidence of this form is not known; however, it occurs most frequently in children exposed through contact with other children or pets. Three types of tinea capitis exist: black dot, gray patch, and favus. frequently causes black dot tinea capitis and is the predominant variant observed in the U.S. Gray patch tinea capitis occurs in epidemic and endemic forms; however, the epidemic form is no longer documented in the U.S. The endemic form, which is caused by , is often spread by cats and dogs. Favus, which rarely occurs in the U.S., is characterized by spores, air spaces, and fragmented hyphae, and occurs more frequently in Eastern Europe and Asia.

Black dot tinea capitis is often asymptomatic initially. An erythematous, scaling patch on the scalp enlarges over time, and alopecia occurs. Hairs within the patches break, and a black dot (caused by detritus within the follicular opening) appears. If black dot tinea capitis is left untreated, the alopecia and scarring may be permanent. On occasion, the lesion may change and become elevated, tender, highly inflamed nodules known as . Kerion formation is due to an immune response to the fungus. Lymphadenopathy may occur with kerion. Gray patch tinea capitis presents as circular patches of alopecia with prominent scaling. Kerion formation may occur with gray patch tinea capitis infection.

Tinea capitis must be treated with systemic antifungal agents, since topicals cannot penetrate the hair shaft. Adjunctive treatment with antifungal shampoos may be recommended. Asymptomatic carriers of dermatophytes may be a source of reinfection. Sharing of fomites such as hats, combs, and brushes should be avoided. Differential diagnosis includes alopecia areata, atopic dermatitis, bacterial infection, psoriasis, and seborrheic dermatitis.

This disorder, also known as , is caused most frequently by dermatophytes, but nondermatophytes and species also can cause it. Annually, more than 2.5 million people in the U.S. are treated for tinea unguium. Affected nails often become thick, rough, yellow, opaque, and brittle. The nail may separate from the nail bed, and the dermis surrounding the infected nail may be hyperkeratotic. Risk factors include diabetes, trauma, family history, tinea pedis, smoking, extended periods of water exposure, and immunodeficiency. Differential diagnosis includes psoriasis, eczema, lichen planus, and trauma. Treatment requires oral therapy for an extended period, at least 6 to 12 weeks, depending upon the location of the infection. Failure rates with oral therapy typically are high, and topical treatment generally is not effective.

Tinea incognito is a dermatophyte infection that is modified because of treatment with a corticosteroid. Margins may be lost, and the area may be more widespread. Tinea incognito requires a thorough patient history and should be considered when a corticosteroid has been used to treat a rash that appeared to have cleared, but returned unresolved.

Yeast Infections

is part of normal body flora, but it is also a common cause of yeast infections. When the normal balance of flora is disturbed, an acute infection may occur. Risk factors include antibiotics, corticosteroids, diabetes, obesity, immunosuppression, and immunodeficiency. Additionally, thrives in warm, moist conditions. An infection often presents as red lesions with accompanying satellite papules and pustules. Common areas of infection are the mouth and genital region. Differential diagnosis includes tinea corporis.

Treatment of Fungal Skin Infections

Tinea pedis, tinea corporis, and tinea cruris generally respond well to topical therapy. Many of these treatments are available as nonprescription formulations. Commonly used topical therapies are described in . Topical agents are available as ointments, creams, powders, and aerosols, and are well-tolerated overall. Rare cases of mild skin irritation, burning, itching, or dryness have been reported. Drug-drug interactions are unlikely with topical therapy.

Multiple combination products incorporating an antifungal plus a corticosteroid are available. Combination therapy with antifungals and corticosteroids is not currently recommended in clinical guidelines. Clinical cure rates have been demonstrated for combination therapy; however, the quality of the studies was poor owing to imprecision and bias, and relapse rates could not be assessed.

Patient adherence may be affected by the product chosen. Therefore, the selection of a drug or product should be made based on the patient’s daily habits and activities, as well as patient-specific characteristics such as concomitant disease states, age, and drug sensitivities.

Oral therapy can be recommended for the treatment of tinea pedis, tinea corporis, and tinea cruris if the infection is extensive, severe, or recalcitrant. See . However, tinea capitis must be treated with oral antifungal therapy, since topical agents do not penetrate the hair shaft, and tinea unguium responds better to oral therapy than to topical treatment.

There are currently two FDA-approved pediatric treatment options for tinea capitis: griseofulvin and terbinafine. Griseofulvin is available as a suspension and as ultramicrosize tablets, but the tablets may be preferred, given the bitter taste of the suspension. For griseofulvin, there is some discrepancy regarding treatment duration for tinea capitis. Manufacturer labeling recommends 4 to 6 weeks, but other sources advise 6 to 12 weeks, and possibly up to 16 weeks. The American Academy of Pediatrics recommends that griseofulvin be continued for 2 weeks after clinical resolution of the infection. In 2007, terbinafine was approved to treat tinea capitis in patients aged 4 years and older. Terbinafine is dosed according to weight and is given once daily for 6 weeks. Off-label uses of itraconazole syrup (5 mg/kg for 4 weeks) and fluconazole (6 mg/kg daily for 3-6 weeks or 6 mg/kg once weekly) are alternative therapies. Because of increasing resistance to griseofulvin, alternative regimens may be preferred for the treatment of tinea capitis; however, griseofulvin remains the drug of choice for kerion and when the etiologic agent is a species.

There are several different oral treatment approaches for onychomycosis. Oral griseofulvin, terbinafine, itraconazole, or fluconazole may be useful, but dosages and treatment duration vary according to the location of the infection (e.g., toenails or fingernails). These antifungal therapies may be effective only if the onychomycosis is caused by dermatophytes; if is the etiologic agent, the infection may be resistant to oral antifungal therapy. Fluconazole is not approved for the treatment of onychomycosis, but pulse dosing may be used off-label (150-300 mg once a week for 3-6 months for fingernails or 6-12 months for toenails). Some researchers believe that oral antifungal therapy should be continued past the recommended treatment duration, at least until the infected nail is replaced by normal growth; however, this may take up to 9 to 12 months.

The use of the oral antifungal agents is not without side effects or significant drug interactions.Common adverse effects of griseofulvin include rash, headache, nausea and vomiting, and photosensitivity; additionally, long-term use of griseofulvin may result in hepatotoxicity. Notable drug interactions with griseofulvin include barbiturates, alcohol, cyclosporine, oral contraceptives, aspirin, and warfarin. Adverse effects of itraconazole include diarrhea, rhinitis, dyspepsia, pruritus, and hypertension. Notable drug interactions with itraconazole include terfenadine, astemizole, diazepam, oral triazolam, oral midazolam, cisapride, and hydroxymethyl glutaryl coenzyme A reductase inhibitors. Fluconazole may cause nausea and vomiting, rash, abdominal pain, and changes in taste. Like itraconazole, fluconazole has many drug interactions and should also be avoided in patients with renal impairment or hepatic disease. All oral antifungals require routine liver function tests.

Good skin care, including regular bathing and complete drying of the skin, is essential for preventing fungal skin infections. Prolonged exposure of the affected area(s) to moisture should be avoided. To prevent the recurrence of tinea pedis, walking barefoot in areas such as public bathrooms, locker rooms, and showers should be avoided. Affected individuals should also consider nonocclusive shoes, absorbent socks, and powder to control the moisture content.

When tinea capitis is confirmed, all contaminated combs, brushes, hats, and bedding should be cleaned. Diagnosed children may return to school once treatment of tinea capitis has begun; however, the sharing of grooming utensils, hats, and bedding should be avoided for at least 14 days.


Proper identification and treatment of fungal skin infections remains a growing health concern. Pharmacists should refer patients with suspected tinea infections to their primary care provider for diagnosis confirmation, and then work in collaboration to effectively manage the infection with pharmacologic and nonpharmacologic treatment recommendations. Pharmacists are well positioned to encourage proper use of and adherence to lengthy treatment regimens. Since patient adherence may be affected by product selection, the pharmacist should consider patient characteristics and lifestyle to ensure that the appropriate product and formulation is chosen.

1. Newton GD, Popovich NG. Fungal skin infections. In: Krinsky DL, Berardi RR, Ferreri SP, et al, eds. . 17th ed. Washington DC: American Pharmacists Association; 2012:757-771.2. Goldstein AO, Smith KM, Ives TJ, Goldstein B. Mycotic infections. Effective management of conditions involving the skin, hair, and nails. . 2000;55(5):40-52,45-47,51-52.3. Robinson J. Fungal skin infections in children. . 2012;27:52-54,56,58.4. Hainer BL. Dermatophyte infections. . 2003;67:101-108.5. Ely JW, Rosenfeld S, Seabury Stone M. Diagnosis and management of tinea infections. . 2014;90:702-710.6. Vander Straten MR, Hossain MA, Ghannoum MA. Cutaneous infections: dermatophytosis, onychomycosis, and tinea versicolor. . 2003;17:87-112.7. Flint WW, Cain JD. Nail and skin disorders of the foot. . 2014;98:213-225.8. Hawkins DM, Smidt AC. Superficial fungal infections in children. . 2014;61:443-455.9. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for superficial mycotic infections of the skin: tinea capitis and tinea barbae. . 1996;34:290-294.10. Fuller LC, Child FJ, Midgley G, Higgins EM. Diagnosis and management of scalp ringworm. . 2003;326:539-541.11. Clinical Pharmacology [online database]. Tampa, FL: Elsevier/Gold Standard; 2014.12. El-Gohary M, van Zuuren EJ, Fedorowicz Z, et al. Topical antifungal treatments for tinea cruris and tinea corporis. . 2014;(8):CD009992.13. Lexicomp Online [online database]. Hudson, OH: Wolters Kluwer Health; 2015.14. Tinea capitis. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. . 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:662.

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Tinea Pedis:

“After all that, Tannehill is back in command in Miami—not that he ever wasn’t.”

The Dolphins wanted to make sure Tannehill knew they were not looking to replace him. This team is Tannehill’s, and that was never a question mark within the doors of the Dolphins’ facilities - no matter how much discussion there has been (and is) outside the franchise about Tannehill’s status.

Breer quotes Dolphins head coach Adam Gase, “‘I really think his thought was— don’t waste the draft pick ,’ Gase said. ‘He focused on work and bringing the same intensity he does every day. He’s very competitive. He’s not going to bat an eye at any of those things. He just keeps going. If there’s some kind of internal thing going on, you’re not going to know. He’s not going to show his cards. So I never worried about it.’”

The rookie and the vet. passes along some words of wisdom to

Tannehill and Gase seem to have a relationship we have not seen between head coach and quarterback in Miami in the recent past. They trust each other and there is an open communication between the two. Tannehill understood what the team was doing, and he also understood that he was going to come back and be the best quarterback for this team - hoping the team did not “waste the draft pick,” by selecting a quarterback who was not going to play.

The Dolphins opened their veteran minicamp on Tuesday, with Tannehill clearly in charge of the offense - and the team. “It just helps you make quicker decisions,” Dolphins quarterback coach Bo Hardegree said of Tannehill’s development last year as he remained around the team despite the injury that held him out all season. “The big thing at the quarterback position is being able to play fast and think less, and just go out and react, and knowing the offense which, our quarterbacks … Being in his third year, he is handling all of the Mike points. He’s up there getting everybody lined up. We’re rolling, trying to play fast and he’s doing a really good job of that.”

“Ryan does a great job of not only relating to the guys on the offense – talking to the guys on the offense – but getting over and talking a little trash to the guys on defense,” wide receiver Kenny Stills said of Tannehill and his influence across the team. “(He’s) not feeling like he’s uncomfortable to go over there and talk some trash and get things going if we need that spark in practice. It differs. It differs by quarterback.”

Free agent addition, wide receiver Danny Amendola , said of Tannehill, “I think he’s a good quarterback. We’ve only been working together for a short time so I’m trying to get better. I’m trying to get on the same page as him, trying to listen to him, what he likes, what he wants and be there for him.”

He continued, “Your quarterback is a natural leader. He’s the one vocalizing the play calls on the field. There’s one quarterback. I feel like we have a great quarterback in Ryan and he’s doing a great job.”

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