Potential use of microwave technology in dermatology.

BACKGROUND: Microwaves are used in medicine for diagnostics, and treatment of cancer. Recently, novel microwave devices (Swift®, Emblation Ltd, UK and miraDry®, Miramar Labs Inc., CA) have been cleared by the FDA and Health Canada for various dermatological conditions. OBJECTIVE AND METHODS: To review the dermatological use of microwave-based treatments (plantar warts, corns, actinic keratosis, dermatophytosis, axillary hyperhidrosis, osmidrosis, and hidradenitis suppurativa). Clinical trials, case reports, or in vitro studies for each condition are summarized. RESULTS AND CONCLUSION: Microwaves are a promising alternative therapy for cutaneous warts, actinic keratosis, axillary hyperhidrosis, and osmidrosis, with favorable safety profiles. However, patients with hidradenitis suppurativa have had negative clinical outcomes. Limited treatment of corns showed good pain reduction but did not resolve hyperkeratosis. A preliminary in vitro study indicated that microwave treatment inhibits the growth of T. rubrum. We present the first case of toenail onychomycosis successfully treated with microwaves. Despite the advancements in the use of microwaves, the mechanism of action in non-ablative treatment is not well understood; further research is needed. More high-quality randomized clinical trials with larger groups and long follow-up periods are also required to evaluate the clinical benefits and possible adverse effects of microwaves in treating dermatological conditions.

Outcomes following stoma formation in patients with spinal cord injury.

AIM: The formation of a diverting stoma of the bowel in patients with spinal cord injury (SCI) is a useful option in managing problems associated with prolonged bowel care, pressure ulcers and neurogenic bowel. This descriptive study examines surgical outcomes and the effect on an individual's health-related quality of life (HrQoL) in this complex group of patients. METHODS: Data were retrospectively collected in all patients with SCI who underwent a diverting stoma at Prince of Wales Hospital, Sydney, between January 2013 and January 2018 via a self-report questionnaire developed specifically for the study. RESULTS: Forty-three individuals were identified of whom 26 responded. 73% were men with a mean age of 45 years. The reasons for stoma formation included sacral pressure ulcer (50%), prolonged bowel care (35%), faecal incontinence (19%), constipation (8%), autonomic dysreflexia (8%), carer difficulties (8%) and haemorrhoids (4%). 76% of patients reported an improvement in HrQoL with 72% scoring their satisfaction with a stoma ≥ 8/10. CONCLUSION: While stoma formation is often seen as a treatment of last resort, our study has shown that it is an effective management option for a number of conditions post-SCI. It can improve HrQoL and has a high level of satisfaction amongst patients. Ideally, patients who could potentially benefit from a stoma should be identified early and receive appropriate education and counselling to help facilitate informed and timely decision-making and reduce adverse bowel related impact on quality of life and adjustment post-SCI.

The prevalence of unsuspected onychomycosis and its causative organisms in a multicentre Canadian sample of 30 000 patients visiting physicians' offices.

BACKGROUND: Onychomycosis is difficult to treat and a concern for many patients. Prevalence estimates of onychomycosis in North American clinic samples have been higher than what has been reported for general populations. OBJECTIVE: A large, multicentre study was conducted to estimate the prevalence of toenail onychomycosis in the Canadian population. METHODS: Patients were recruited from the offices of three dermatologists and one family physician in Ontario, Canada. Nail samples for mycological testing were obtained from normal and abnormal-looking nails. This sample of 32 193 patients includes our previous published study of 15 000 patients. RESULTS: Abnormal nails were observed in 4350 patients. Of these, the prevalence of culture-confirmed toenail onychomycosis was estimated to be 6.7% (95% CI, 6.41-6.96%). Following sex and age adjustments for the general population, the estimated prevalence of toenail onychomycosis in Canada was 6.4% (95% CI, 6.12%-6.65%). The distribution of fungal organisms in culture-confirmed onychomycosis was 71.9% dermatophytes, 20.4% non-dermatophyte moulds and 7.6% yeasts. Toenail onychomycosis was four times more prevalent in those over the age of 60 years than below the age of 60 years. CONCLUSION: The present data highlights that onychomycosis may be a growing medical concern among ageing patients.

Comparison of visual assessments versus planimetry assessments in a large-scale clinical trial of onychomycosis.

BACKGROUND: Computerized nail planimetry is an objective means of accurately assessing affected nail areas, versus the standard visual estimation method. However, no published comparison of visual assessment with planimetry is currently available on onychomycosis to support this recommendation. OBJECTIVES: This article evaluates efficacy based on visual assessment compared to planimetry measures during the course of an 84-week large-scale, single-site trial of subungual dermatophyte onychomycosis, to determine the validity of planimetry versus visual assessment. METHODS: Visually assessed percentage of affected area of the target toenail was compared with planimetry calculated measurements made from digital photographs. RESULTS: Comparison showed good statistical agreement of visual and planimetry measures based on correlation coefficient. Visual and planimetry assessments at week 84 were within 10% of each other in 92% of cases, and within 5% of each other in 74% of comparisons. However, errors in visual assessment artificially inflated the cure rates by 9% and 11% at weeks 84 and 48, respectively. Furthermore, the significant difference in effective cure between regimens using visual methods loses significance when planimetry measures are used. CONCLUSIONS: The results suggest that objective measures such as planimetry will reduce the impact of visual assessment errors, and techniques to increase the standardization of onychomycosis assessment are warranted.

The use of an intermittent terbinafine regimen for the treatment of dermatophyte toenail onychomycosis.

OBJECTIVE: To compare the efficacy and safety of intermittent terbinafine with standard courses of terbinafine and itraconazole for dermatophyte toenail onychomycosis. DESIGN: Data from a Canadian study of continuous terbinafine (CTERB) and intermittent itraconazole (III) was compared to an intermittent terbinafine regimen (TOT) using similar protocol to the randomized study. INTERVENTIONS: Terbinafine 250 mg/day for 4 weeks followed by 4 weeks of no terbinafine and then an additional 4 weeks of terbinafine 250 mg/day (TOT); terbinafine 250 mg/day for 12 weeks (CTERB); itraconazole pulse of 200 mg twice daily for 7 days on, 21 days off, three pulses given (III). RESULTS: At 72 weeks, mycological cure rates (negative KOH and culture) were 36 of 43 (83.7%), 25 of 32 (78.1%), and 17 of 30 (56.7%), for the TOT, CTERB, and III groups, respectively (P = 0.01 for TOT vs. III). Effective cure rates (simultaneous mycological cure and < or =10% nail plate involvement) were 34 of 43 (79.1%), 21 of 32 (65.6%), and 11 of 30 (36.7%), respectively (P < 0.001 for TOT vs. III; P = 0.02 for CTERB vs. III). No significant differences in effective and mycological cure rates were noted between the two terbinafine groups. Adverse events reported were similar to those reported in the respective package inserts. Most adverse events were mild to moderate, transient, and did not require interruption of the drug regimens. No serious adverse events were reported. CONCLUSIONS: A TOT intermittent terbinafine regimen provided similar efficacy and safety to the gold standard continuous terbinafine regimen and better effective cure rates than pulse itraconazole therapy.

The efficacy and safety of terbinafine in children.

Terbinafine is an allylamine antifungal agent that has been effective and safe in the treatment of superficial and some deep mycotic infections in adults. An increasing amount of data is available where terbinafine has been used in the paediatric population to treat superficial fungal infections, in particular tinea capitis. The data suggest that terbinafine is effective and safe using treatment regimens that involve short duration therapy, leading to an increased compliance and providing a cost-effective means of treating paediatric superficial fungal infections such as tinea capitis. Terbinafine has been approved for the treatment of tinea capitis in many countries worldwide, and provides good efficacy rates for Trichophyton tinea capitis using shorter regimens than the gold standard griseofulvin. The adverse events profile for children is similar to that in adults with few adverse effects associated with its use. The evidence favours the use of terbinafine in the treatment of superficial infections in children.

Utility of inoculum counting (Walshe and English criteria) in clinical diagnosis of onychomycosis caused by nondermatophytic filamentous fungi.

Opportunistic onychomycosis caused by nondermatophytic molds may differ in treatment from tinea unguium. Confirmed diagnosis of opportunistic onychomycosis classically requires more than one laboratory analysis to show consistency of fungal outgrowth. Walshe and English in 1966 proposed to extract sufficient diagnostic information from a single patient consultation by counting the number of nail fragments positive for inoculum of the suspected fungus. Twenty fragments were plated per patient, and each case in which five or more fragments grew the same mold was considered an infection by that mold, provided that compatible filaments were also seen invading the nail tissue by direct microscopy. This widely used and often recommended method has never been validated. Therefore, the validity of substituting any technique based on inoculum counting for conventional follow-up study in the diagnosis of opportunistic onychomycosis was investigated. Sampling of 473 patients was performed repeatedly. Nail specimens were examined by direct microscopy, and 15 pieces were plated on standard growth media. After 3 weeks, outgrowing dermatophytes were recorded, and pieces growing any nondermatophyte mold were counted. Patients returned on two to eight additional occasions over a 1- to 3-year period for similar examinations. Onychomycosis was etiologically classified based on long-term study. Opportunistic onychomycosis was definitively established for 86 patients. Counts of nondermatophyte molds in initial examinations were analyzed to determine if they successfully predicted both true cases of opportunistic onychomycosis and cases of insignificant mold contamination. There was a strong positive statistical association between mold colony counts and true opportunistic onychomycosis. Logistic regression analysis, however, determined that even the highest counts predicted true cases of opportunistic onychomycosis only 89.7% of the time. The counting criterion suggested by Walshe and English was correct only 23.2% of the time. Acremonium infections were especially likely to be correctly predicted by inoculum counting. Inoculum counting could be used to indicate a need for repeat studies in cases of false-negative results from laboratory direct microscopy. Inoculum counting cannot serve as a valid substitute for follow-up study in the diagnosis of opportunistic onychomycosis. It may, nonetheless, provide useful information both to the physician and to the laboratory, and it may be especially valuable when the patient does not present for follow-up sampling.

Epidemiology and prevalence of onychomycosis in HIV-positive individuals.

BACKGROUND: Patients who are human immunodeficiency virus (HIV) positive are predisposed to the development of infections including tinea pedis and onychomycosis. While smaller studies have been reported, there has been no large study evaluating the prevalence of onychomycosis in HIV-positive individuals, or comparing the development of onychomycosis in a typical temperate area with that in a typical tropical area. METHODS: HIV-positive individuals were evaluated at five clinics: four in Ontario, Canada and one in Sao Paulo, Brazil. The subjects were asked questions to determine the epidemiology of onychomycosis in HIV-positive individuals. The feet were examined and nail material was obtained for mycologic examination to determine the causative organism of onychomycosis. RESULTS: A total of 500 subjects were examined (415 men and 85 women; age (mean +/- SE), 39 +/- 0.4 years; 400 Canadian, 100 Brazilian). The racial origins of the Canadian patients were: Caucasian, 83.8%; Asian, 4.3%; African-American, 8.1%; Hispanic, 3.3%; American Indian, 0.3%. The Brazilian origins were: Caucasian, 68.7%; African, 18.1%; mixed race, 13.3%. Abnormal appearing nails and mycologic evidence of onychomycosis were present in 200 (40.0%) and 116 (23.2%), respectively, of 500 subjects. The prevalence of onychomycosis in the Canadian and Brazilian samples was 24.0% (96 of 400) and 20.0% (20 of 100), respectively. The projected prevalence of onychomycosis in HIV-positive individuals in Canada was 19.9% (95% CI: 16.0-23.9%) after taking into account the age and sex distribution of HIV-positive individuals in the population. When nails appeared clinically abnormal, the prevalence of onychomycosis was 50.5% (Canada, 51.3%; Brazil, 45.5%). For comparison, published data indicate that the prevalence of onychomycosis in immunocompetent individuals living in Canada is 6.9%. The clinical presentation of onychomycosis for the whole sample (n=500) was: distal and lateral subungual onychomycosis (DLSO), 20.0%; white superficial onychomycosis (WSO), 3.6%; proximal subungual onychomycosis (PSO), 1.8% (Canadian and Brazilian samples: DLSO 21.2% vs. 15.0%, WSO 3.3% vs. 5.0%, and PSO 1.5% vs. 3.0%). The distribution of the causative fungal organisms was: dermatophytes: Candida species: nondermatophyte molds, 73:2:2 (Canadian and Brazilian samples: dermatophytes 95.5% vs. 90.9%, Candida species 3.0% vs. 0%, and nondermatophyte molds 1.5% vs. 9.0%). The use of protease inhibitors, reverse transcriptase inhibitors, or oral antifungal agents did not make a significant difference in the prevalence of onychomycosis for both the Canadian and Brazilian groups. Patients with onychomycosis were aware of their abnormal appearing nails (chi2(1)=69.7, P<0.001), embarrassed by the appearance of their nails (chi2(1)=29.7, P<0.001), and took measures to hide their nails from other individuals. A higher proportion of individuals with onychomycosis experienced discomfort compared with those without the disease (chi2(1)=9.0, P=0.003). Also, individuals who experienced pain in the nail unit were more likely to have onychomycosis (risk odds ratio (ROR), 2.2; 95% CI: 1.0-4.7, P=0.05). CONCLUSIONS: The prevalence of onychomycosis in HIV-positive individuals in the sample of 500 patients was 23.2%. In the Canadian (n=400) and Brazilian (n=100) samples, the corresponding figures were 24% and 20%, respectively, with the predominant causative organisms being dermatophytes. The projected prevalence of onychomycosis in HIV-positive Canadians is 19.9%. Predisposing factors include a CD4 count of approximately 370, a positive family history of onychomycosis, a history of tinea pedis, and walking barefoot around pools. Onychomycosis can be symptomatic, a source of embarrassment, and a potential cause of morbidity.

Prevalence and epidemiology of onychomycosis in patients visiting physicians' offices: a multicenter canadian survey of 15,000 patients.

A prospective, multicenter study to determine the epidemiology of onychomycosis was performed in the offices of 3 dermatologists and 1 family physician in Ontario, Canada. In the sample of 15,000 patients, abnormal-appearing nails were observed in 2505 persons (16. 7%). There were 1199 patients (8%) with toenail or fingernail onychomycosis confirmed on mycologic examination, with 1137 patients (7.6%) who had only pedal onychomycosis, 40 patients with toenail and fingernail onychomycosis (0.27%), and 22 patients (0.15%) with only fingernail onychomycosis. The condition was more common in male patients (P <.0001) and older persons (P <.0001). The ratio of onychomycosis in toenails/fingernails was 19:1. When onychomycosis was present in toenails, the ratio of distal/lateral subungual onychomycosis (DLSO) to white superficial onychomycosis to proximal subungual onychomycosis was 360:59:1. The extent of DLSO in toenails was mild (< or =25% nail involvement), moderate (26%-74% disease), and severe (> or =75% nail involvement) in 27.6%, 39.9%, and 32.5% of patients, respectively. After adjusting for the age and sex distribution of the general population, the projected rate of onychomycosis in Canada is 6.5% (95% confidence interval [CI], 6. 1%-6.9%). The organisms causing toenail onychomycosis were 90.5% dermatophyte, 7.8% nondermatophyte molds, and 1.7% Candida spp. The corresponding organisms causing fingernail onychomycosis were 70.8%, 0%, and 29.2%, respectively. In a large sample of 15,000 patients, abnormal-appearing nails were present in 17% of the sample with mycologic evidence of toenail or fingernail onychomycosis in 8%. The projected prevalence of onychomycosis in Canada is 6.5% (95% CI, 6. 1%-6.9%).

The epidemiology of onychomycosis: possible role of smoking and peripheral arterial disease.

BACKGROUND: Onychomycosis is a relatively common condition the aetiology of which appears to be multifactorial, with both genetic and acquired factors being responsible. In our clinical practice we have observed that smokers and individuals with peripheral arterial disease may have an increased prevalence of onychomycosis compared to normal individuals. PATIENTS AND METHODS: Patients attending a vascular clinic in a hospital were asked about a history of smoking and peripheral arterial disease. The lower extremity was assessed for peripheral arterial disease. Material was obtained from toenails for mycological evaluation. RESULTS: Two hundred and fifty-four patients (male 146, female 108; age, mean +/- standard error, 66.6 +/- 0.8 years) were enrolled. Abnormal-appearing nails and onychomycosis were present in 49.2% and 22.4% of patients, respectively. Factors associated with onychomycosis included, increasing age (risk odds ratio [ROR] 1.05, P = 0.002), male gender (ROR 1.7, P = 0.09), smoking (packs per day) (ROR 1.9, P = 0.02) and peripheral arterial disease (ROR 4.8, P = 0.02). CONCLUSIONS: The factors predisposing to the development of onychomycosis are multifactorial. Both smoking (number of packs of cigarettes consumed per day) and peripheral arterial disease are independent predictors of onychomycosis. Awareness of these factors may help in the prevention of onychomycosis and the optimal management of this disease.

Fourier transform infrared spectroscopy investigations of protein structure.

Infrared spectroscopy can provide insight into protein structure. This technique is sensitive to the backbone amide arrangement of peptide and protein molecules. In many cases, complementary as well as more expansive information is obtained as opposed to information obtained by other methods that examine the molecule's environmental surroundings, require molecular probes, or perhaps cannot investigate the molecule in its native environment. The foundation for spectroscopic differences between the various secondary structures arises not only from geometrical differences and hydrogen bond variations but also transition dipole coupling between neighboring oscillators. Theoretical predictions of protein spectra have been made using normal mode analysis and combined with experimental data. At present the amide I band has provided the most insight into secondary structure. Even more convincing results are obtained when both H2O and D2O are used as solvents. Recent advances in computerized technology and mathematical techniques have expanded the potential contributions of infrared spectroscopy in the area of protein structural determination. However, the limitations of resolution enhancement and curve-fitting techniques must be taken into consideration. The parameters must be carefully and optimally chosen and evaluated on a case-by-case basis. The subjectivity of these techniques makes a thorough understanding of the algorithms necessary, especially those commercially available. Infrared spectroscopy continues to provide insight into protein and peptide structures under biologically relevant conditions that enable the structure-function relationships for such molecules to be better understood.

Cardiovascular actions of atrial natriuretic factor in sheep with cardiac failure.

The present study examines in detail the short-term cardiovascular actions of atrial natriuretic factor (ANF) in sheep with experimental low-output cardiac failure. Five conscious sheep, surgically implanted with a ventricular pacing wire, were paced at 220 beats/min for 14 days. Most clinical symptoms of congestive heart failure (CHF) were apparent after the 14 days, characterized by low cardiac output, high venous pressure, increased total peripheral resistance, increased plasma levels of ANF, noradrenaline, arginine vasopressin and renin, and marked fluid retention. On day 14 of pacing, intravenous infusion of ANF at 100 micrograms/h for 60 min restored cardiac output to prepacing values and reduced both total peripheral resistance and right atrial pressure. These effects were sustained throughout the infusion period. No change was seen in blood pressure, plasma renin, or noradrenaline levels. These hemodynamic changes, produced by short-term infusion of ANF, contrasted with those seen in normal sheep, where there was a fall in cardiac output with increased total peripheral resistance. These changes reflect a return toward normal of the left ventricular function curve. This is the first study to report that ANF improves cardiac function in conscious sheep with CHF, primarily by a vasodilator action to reduce cardiac preload, and suggests that ANF may be useful in treating the hemodynamic effects associated with cardiac failure.