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.

Finasteride for hair loss: a review.

BACKGROUND AND OBJECTIVES: Finasteride 1 mg/day is indicated for androgen-dependent conditions such as male androgenetic alopecia (AGA). METHODS: The literature is comprehensively summarized on the pharmacodynamics, pharmacokinetics, mechanism of action, and metabolism of finasteride. Pairwise and network meta-analyses were performed to assess the efficacy of finasteride reported in clinical trials. The adverse events profile is described along with the post-marketing reports. RESULTS AND CONCLUSION: Finasteride 1 mg/day significantly increased total hair count compared to placebo after 24 weeks (mean difference = 12.4 hairs/cm2, p < .05), and 48 weeks (mean difference = 16.4 hairs/cm2, p < .05). The efficacy of the two doses of finasteride (5 mg/day and 1 mg/day) and topical finasteride (1% solution) were not significantly different. The most commonly reported sexual events include erectile dysfunction and decreased libido. Increasing patient complaints and analysis of the FAERS database led to the inclusion of depression in the FDA label in 2011, as men were found to be at a risk of suicide due to the persistent sexual side effects, commonly termed as post-finasteride syndrome. Finasteride is shown to be reasonably tolerated in both men and women; however, patients need to be educated about the possible short- and long-term side-effects.

Minoxidil: a comprehensive review.

Topical minoxidil (5% foam, 5% solution, and 2% solution) is FDA-approved for androgenetic alopecia (AGA) in men and women.Mechanism of action: Minoxidil acts through multiple pathways (vasodilator, anti-inflammatory agent, inducer of the Wnt/ß-catenin signaling pathway, an antiandrogen), and may also affect the length of the anagen and telogen phases.Pharmacokinetics: Approximately 1.4% of topical minoxidil is absorbed through the skin. Minoxidil is a prodrug that is metabolized by follicular sulfotransferase to minoxidil sulfate (active form). Those with higher sulfotransferase activity may respond better than patients with lower sulfotransferase activity.Clinical efficacy (topical minoxidil): In a five-year study, 2% minoxidil exhibited peak hair growth in males at year one with a decline in subsequent years. Topical minoxidil causes hair regrowth in both frontotemporal and vertex areas. The 5% solution and foam were not significantly different in efficacy from the 2% solution.Oral and Sublingual minoxidil (not FDA approved; off-label): After 6 months of administration, minoxidil 5 mg/day was significantly more effective than topical 5% and 2% in male AGA. Low-dose 0.5-5 mg/day may also be safe and effective for female pattern hair loss and chronic telogen effluvium. Sublingual minoxidil may be safe and effective in male and female pattern hair loss.

Nondermatophyte mould onychomycosis.

Nondermatophyte moulds (NDMs) onychomycosis is often difficult to diagnose as NDMs have been considered contaminants of nails. There are several diagnostic methods used to identify NDMs, however, repeated laboratory isolation is recommended to validate pathogenicity. With NDM and mixed infection (dermatophytes plus NDM) onychomycosis on the rise, accurate clinical diagnosis along with mycological tests is recommended. Systemic antifungal agents such as itraconazole and terbinafine (e.g. pulse regimen: 1 pulse = every day for one week, followed by no treatment for three weeks) have shown efficacy in treating onychomycosis caused by various NDMs such as Aspergillus spp., Fusarium spp., Scopulariopsis brevicaulis, and Onychocola canadensis. Studies investigating topical therapy and devices for NDM onychomycosis are limited. The emergence of antifungal resistance necessitates the incorporation of antifungal susceptibility testing into diagnosis when possible, for the management of recalcitrant infections. Case studies documented in the literature show newer azoles such as posaconazole and voriconazole as sometimes effective in treating resistant NDM onychomycosis. Treatment with broad-spectrum antifungal agents (e.g. itraconazole and efinaconazole) and other combination therapy (oral + oral and/or oral + topical) may be considerations in the management of NDM onychomycosis.

Anterior Vertebral Body Tethering for Adolescent Scoliosis with Growth Remaining: A Retrospective Review of 2 to 5-Year Postoperative Results.

BACKGROUND: Anterior vertebral body tethering (VBT) is an early treatment option for progressive scoliosis in pediatric patients, allowing for continued deformity correction during normal growth. We report postoperative radiographic and clinical outcomes for patients treated with VBT. METHODS: This clinical and radiographic retrospective review of 31 consecutive patients included an analysis of preoperative, perioperative, and postoperative details, including the Lenke classification; Cobb angle measurements of the proximal thoracic, main thoracic, and lumbar curves; the sagittal profile; and skeletal maturity. Successful outcomes were defined by a residual curve of ≤30° in skeletally mature patients who did not undergo a posterior spinal fusion (PSF). RESULTS: Of the 31 patients treated, 29 met the inclusion criteria, and 2 were lost to follow-up. The mean patient age (and standard deviation) at the time of the surgical procedure was 12.7 ± 1.5 years (range, 10.2 to 16.7 years), with most patients classified as Risser grade 0 or 1 (52%) and Sanders stage 3 (32%). A mean of 7.2 ± 1.4 vertebral levels were instrumented, with a minimum preoperative Cobb angle of 42°. At the latest follow-up, 27 patients had reached skeletal maturity (Sanders stage ≥7) and 20 patients exhibited a curve magnitude ≤30°, for a success rate of 74%. A suspected broken tether occurred at ≥1 level in 14 patients (48%). Two patients underwent PSF and 4 had tether revision. The overall revision rate was 21% (6 of 29). CONCLUSIONS: This study shows the success and revision rates as well as the impact of a suspected broken tether on the procedural success of VBT. Despite our patient population being slightly more mature at the time of the surgical procedure compared with previous studies, we had a higher success rate and a lower revision rate. A PSF was avoided in 93% of patients, indicating that VBT may be a reliable treatment option for adolescent scoliosis in skeletally immature individuals. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Hansen's disease: An unusual presentation.

Hansen's disease can present with varied and subtle symptoms which can be missed. A middle-aged gentleman presented with swelling of face and hands. Detailed examination and investigations confirmed borderline tuberculoid leprosy with lepra reaction. A high index of suspicion with vigilance can help to make an early diagnosis in this potentially treatable condition.

T-antigen (Gal ß3 GaINAc α-) containing glycoproteins of human reace.

Desialation of cell surface glycoconjugates due to bacterial or viral infection can expose epitopes like T-antigenic structure which can also occur during oncological transformations. Human platelet plasma membrane glycoproteins were isolated by jacalin affinity chromatography. Potential T-antigen containing glycoproteins which were not reported before could be identified on the Western blot using peanut agglutinin-horse radish peroxidase (PNA-HRP) after neuraminidase treatment. Alpha-galactosyl epitopes recognized by anti-gal were found to be absent in human platelet plasma membrane glycoproteins. Under the experimental conditions employed, the Gp IIbα was identified most rich in T-antigenic structures. Probable role of exposed T-antigenic structures and α-galactosyl epitopes in pathological conditions is discussed. The identity of major glycoprotein bands was confirmed by differential lectin-binding studies with Concanavalin A on the Western blot. The higher binding affinity of jacalin for T-antigenic structures when compared to PNA enabled the isolation and detection of the antigen containing platelet surface glycoproteins which were not reported before.

Effects of cryopreservation of immune responses. XI. Heightened secretion of tumor necrosis factor-alpha by frozen human peripheral blood mononuclear cells.

In view of the wide usage of frozen PBMCs as stem cell support following high-dose chemo- and/or radiotherapy, and the pleiotropic activities of tumor necrosis factor-alpha (TNF-alpha), the influences of freezing and radiation on LPS-induced TNF-alpha production by human peripheral blood mononuclear cells (PBMCs) were studied. Frozen PBMCs secreted significantly larger quantities of TNF-alpha than fresh cells. Blocking of endogenous IL-10 by neutralization with anti-IL-10 monoclonal antibody resulted in further augmented and prolonged secretion of TNF-alpha by both the fresh and frozen cells. In contrast, addition of exogenous IL-10 to LPS-stimulated cultures inhibited TNF-alpha secretion. In vitro irradiation had an inconsistent effect on TNF-alpha production by the fresh PBMCs. Taken together, these results suggest that the endogenously hypersecreted TNF-alpha is indirectly responsible for the previously reported elevated IL-1-, IL-6-, and IL-10-secreting capabilities of frozen PBMCs. They also indicate that the TNF-alpha induced IL-10 and then down-regulates the monocytes from further TNF-alpha secretion. Considering the vital role played by TNF-alpha in antimicrobial and antitumor activities, in the immune system, and in the pathogenesis of many acute and chronic diseases, the abilities of frozen cells to produce large quantities of TNF-alpha in response to infectious agents could have profound impact on patients receiving such frozen PBMCs as stem cell support following myeloablative therapies.

Reversal of intractable acute severe asthma by first-trimester termination of pregnancy.

A 19-year-old woman was admitted with acute severe asthma in her eleventh week of pregnancy. Despite vigorous therapy, severe hypoventilation and hypoxemia persisted with mechanical ventilation. Termination of pregnancy resulted in dramatic improvement in airflow. Her course was complicated by pneumonia, barotrauma, and atelectasis accompanying her moribund state. Although she immediately improved following abortion (within 2 hr, peak airway pressure fell from > 70 to 38 cmH2O, without change in plateau pressure), superimposed morbidities improved more slowly, and the patient made a complete recovery. The mechanism accounting for this observation is unknown but the rapid improvement following abortion suggests that increased bronchomotor tone predominated inflammatory changes in causing flow limitation.

Effects of cryopreservation on immune responses. X. Decrease in interleukin-12 production by frozen human peripheral blood mononuclear cells is mediated by the endogenously hypersecreted interleukin-10.

The contrasting effects of freezing and radiation on lipopolysaccharide (LPS)-induced interleukin (IL)-10 production by human peripheral blood mononuclear cells (PBMCs) have recently been reported. In view of the potent inhibitory properties of IL-10 on IL-12 secretion and the central role played by IL-12 in the immune system, the influences of freezing and radiation on LPS-induced IL-12 production by PBMCs were studied. Frozen PBMCs secreted significantly smaller amounts of IL-12 than fresh cells. In contrast, the in vitro-irradiated PBMCs produced significantly larger amounts of IL-12. Culture of frozen cells in the presence of exogenous anti-IL-10 antibody resulted in the production of significantly larger amounts of IL-12. These results suggest that the endogenously hyperscreted IL-10 is primarily responsible for the observed decrease in IL-12 released by the frozen cells. They further suggest that the increased amounts of IL-12 secreted by the irradiated PBMCs could account for the previously reported increase in IL-2 and interferon (IFN)-gamma release by the irradiated PBMCs and the radiation-induced immunopotentiation and tumor regression. Considering the pivotal role played by IL-12 in the immune system, and in antimicrobial and antitumor activities, production of only 10% of the normal levels by the frozen cells could have profound impact on patients receiving such frozen PBMCs as stem cell support following myeloablative therapy. Administration of exogenous IL-12 at the time of frozen PBMC transplantations might have a therapeutic value in these patients.

Effects of cryopreservation on immune responses: IX. Stimulus-mediated dichotomy in IL-10 production by frozen human peripheral blood mononuclear cells.

The effects of freezing on phytohemagglutinin (PHA) and lipopolysaccharide (LPS)-induced interleukin-10 (IL-10) production by human peripheral blood mononuclear cells (PBMC) were studied. The freezing process had a divergent effect on the production of IL-10 by PBMC. Frozen PBMC produced significantly smaller amounts of IL-10 in response to PHA stimulation while secreting significantly larger quantities in response to LPS activation. In vitro irradiated PBMC produced significantly smaller amounts of IL-10 in response to both PHA and LPS stimulation. The results indicate that the functional inactivation of a naturally occurring subset of cryosensitive and radiosensitive immunodownregulatory cells is responsible for the observed divergence. They further suggest that, in addition to other mechanisms, a reduction in the secretion of this cytokine synthesis inhibitory factor by the frozen PHA-activated cells could have contributed to the previously reported, augmented IL-2 and IFN-gamma-secreting capabilities of frozen PBMC. The significance of this freezing-induced deviation in IL-10 secretion by PBMC in relation to cancer therapy is discussed.

Comparison of two percutaneous intravenous "midline" catheters in cystic fibrosis.

Administration of intravenous antibiotics in cystic fibrosis has been facilitated by the use of midline catheters; percutaneous lines inserted through a peripheral vein and advanced into a large but noncentral vein. In a randomized study, a 23-gauge silastic catheter (Vygon EC, Cirencester, United Kingdom) was compared with the Hydrocath (Viggo-Spectromed, Swindon, United Kingdom), a 22-gauge hydrophillic coated polyurethane catheter inserted using the Seldinger technique. Fifty eight courses of intravenous antibiotics were given, 28 through the Hydrocath (median age 11 years, range 1.5-17.5 years) and 30 through the silastic catheter, (median age 11 years, range 0.5-17.5). Mean line survival was equal. The Hydrocath took longer to insert and was associated with more pain on insertion. However, administration of antibiotics was easier through the Hydrocath and overall satisfaction was higher in those who had the Hydrocath. Both catheters performed well, but administration of antibiotics was easier through the Hydrocath.

Effects of cryopreservation on immune responses. VIII. Enhanced secretion of interferon-gamma by frozen human peripheral blood mononuclear cells.

The effect of freezing on phytohemagglutinin-induced interferon-gamma (IFN-gamma) production by human peripheral blood mononuclear cells (PBMCs) was studied. The possible mechanisms responsible for the observed effects were also analyzed. Frozen PBMCs produced significantly larger quantities of IFN-gamma than fresh cells. Like the frozen cells, the monocyte- and natural killer cell-eliminated populations of fresh PBMCs also secreted significantly larger quantities of IFN-gamma. In contrast, the freezing process had no enhancing effect on IFN-gamma production by monocyte-depleted PBMCs. Irradiated PBMCs also secreted larger quantities of IFN-gamma. The results suggest that functional inactivation of a subset of cryosensitive suppressor monocytes is associated with an increase in IFN-gamma production by the T lymphocytes. The results provide further evidence that monocytes mediate their suppressive effect through the activation of a subset of radiosensitive, immuno-down-regulatory T cells. The ability of frozen cells to produce larger quantities of IFN-gamma should be of clinical importance. For instance, cancer patients receiving frozen PBMCs as stem cell support (after myeloablative radio/chemotherapy) should benefit from the increased IFN-gamma secretion because of its potent immunoregulatory, microbicidal, and antitumor activities.

Cystic fibrosis in children from ethnic minorities in the West Midlands.

BACKGROUND: We have observed that Doctors often perceive that cystic fibrosis (CF) is exceptionally rare in non-whites, and that this bias has repeatedly resulted in diagnostic delay. We therefore compared the age at diagnosis, genetic features and relative prevalence of CF in non-whites and white patients in the West Midlands. METHODS: Analysis of data on all CF patients diagnosed in childhood and stored in the West Midlands CF register. RESULTS: Sixteen of the 514 children on the register were not of white European extraction, comprising 13 patients whose families originated from the Indian subcontinent, two of mixed AfroCaribbean/white European extraction and one of mixed Pakistani/white European extraction. The median age of diagnosis was similar in the white European and non-white patients (0.42 vs. 0.33 years, 95% CI for the difference of the medians -0.15, 0.37). However, in five cases with typical clinical features the diagnosis appears to have been delayed because of the child's racial origin (median age of diagnosis 3.87 years), and in five others the diagnosis was obvious (two siblings with CF, three had meconium ileus). There was a degree of consanguinity in nine cases. Five patients were homozygous or heterozygous for the delta F508 mutation, but no mutation could be identified in the remaining 11 patients. CONCLUSIONS: The possibility of CF needs to be considered in any patient with relevant clinical problems, regardless of racial origin. These findings need to be considered when planning any mass population screening programme for CF.

Effects of cryopreservation on immune responses: VII. Freezing induced enhancement of IL-6 production in human peripheral blood mononuclear cells.

To better understand the effects of freezing on various immunocompetent cell functions, the interleukin-6 (IL-6)-producing activities of frozen peripheral blood mononuclear cells (PBMCs) from healthy subjects were determined. Frozen, lipopolysaccharide (LPS)-activated PBMCs produced significantly larger quantities of IL-6 than fresh cells. Although elimination of radiosensitive, CD8+ suppressor T cells had no significant effect on PHA-induced IL-6 production by T cells, elimination of CD4+ Leu-8+ suppressor T cell subsets resulted in a significantly enhanced IL-6 secretion. Exogenous addition of prostaglandin E-2 to frozen PBMCs and monocytes inhibited LPS-induced IL-6 production. The results suggest that functional inactivation of a subset of cryosensitive, PGE-2-secreting monocytes is associated with an increase in IL-6 production by the other subset. They also indicate that a subset of CD4+ Leu-8+ T cells might be involved in feedback inhibition of PHA-induced T cell-mediated IL-6 production. The results provide further evidence that the presence of larger quantities of IL-6 in conjunction with increased amounts of IL-1 and IL-2 secreted by the frozen cells may be responsible for the previously reported enhanced immunoglobulin-producing abilities of frozen cells from clinically healthy subjects and from patients with lung cancer.