CpG Oligodeoxynucleotides as TLR9 Agonists

Toll-like receptors (TLRs) are part of the innate immune system, and they belong to the pattern recognition receptors (PRR) family. The PRR family is designed to recognize and bind conserved pathogen-associated molecular patterns, which are not generated by the host and are restricted and essential to microorganisms. TLR9, which recognizes unmethylated CpG (cytosine guanosine dinucleotide), is a very promising target for therapeutic activation. Stimulation of TLR9 activates human plasmacytoid dendritic cells and B cells, and results in potent T helper-1 (T_h1)-type immune responses and antitumor responses in mouse tumor models and in patients. Several pharmaceutical companies, such as Pfizer, Idera, and Dynavax, are developing CpG oligodeoxynucleotides (ODNs) for the treatment of cancer, along with other conditions, such as infections and allergy. CpG ODNs have shown promising results as vaccine adjuvants and in combination with cancer immunotherapy. Several TLR9 agonists are being developed and have entered clinical trials to evaluate their safety and efficacy for the treatment of several hematopoietic and solid tumors. In this review, we discuss the use of CpG ODNs in several phase I and II clinical trials for the treatment of NHL, renal cell carcinoma, melanoma, and non-small cell lung cancer, either alone or in combination with other agents.     

Mirtazapine augmentation for selective serotonin reuptake inhibitor-induced sexual dysfunction: a retropective investigation

The aim of the present study was to retrospectively identify sexual dysfunction changes in the patients under mirtazapine-augmented serotonin reuptake inhibito (SSRI) treatment. The study comprised medical records of 20 outpatients, under mirtazapine-augmented SSRI treatment for their major depressive disorder, who had been selected among the patients that had developed sexual dysfunction to previous treatment as monotherapy, with SSRI for at least six weeks. These drugs were maintained and mirtazapine were added (15-45 mg/day). There was a significant difference in scores between baseline and week 4 or week 8 on the both Hamilton Depression Rating and Arizona Sexual Experience Scale. According to Clinical Global Impression-Improvement, 68.4% of the patients were responders. The use of low-dose mirtazapine as an add-on treatment to SSRIs appears to be an effective and well-tolerated augmenttaion for sexual dysfunction caused by SSRIs.     

Sildenafil use in patients with olanzapine-induced erectile dysfunction

In the present study, we aimed to examine the efficacy of sildenafil in patients with an antipsychotic (olanzapine)-induced erectile dysfunction (ED). The study group comprised 10 patients who experienced ED associated with the use of olanzapine. The patients initially received 50 mg sildenafil at baseline. If clinically indicated, titration up to 100 mg was permitted. All patients were assessed by Clinical Global Impression-Improvement (CGI-I) and International Index of Erectile Dysfunction (IIEF) scales at baseline and weeks 2 and 4. At final assessment, three patients were considered 'very much improved' and four 'much improved' according to CGI-I. Our results suggest that sildenafil use is effective and well-tolerated in patients with olanzapine-induced ED.     

Human papillomavirus-associated digital squamous cell carcinoma: literature review and report of 21 new cases

OBJECTIVE: Our aim was to review the clinical behavior of human papillomavirus (HPV)-associated digital squamous cell carcinoma (SCC). Specifically, we examined evidence for the tumor's (1) infectious origin and spread, (2) response to therapy, and (3) prognosis and metastatic risk. DESIGN: We reviewed and performed data tabulation of all 51 reported cases in the English-language literature and a case series of 23 cases (21 of them not previously reported). We present 2 of the cases in depth. SETTING: We used previously reported cases from MEDLINE and a case series from a single dermatologic operation practice from 1985 to 1999. RESULTS: (1) Of all cases, 10% (7/72) had an antecedent genital dysplasia or carcinoma containing the same HPV subtype as the digital SCC. (2) The rate of recurrence after general surgical therapy was 43% (6/14). After Mohs micrographic surgery the recurrence rate was 13% (2/16) for the cases in the literature, and 26% (6/23) for our case series. (3) Of tumors, 3% (2/72) have been observed to metastasize. CONCLUSIONS: (1) This suggests the possibility of genital-digital spread as a mechanism of tumor genesis. (2) HPV-associated digital SCC is more likely to recur after surgical treatment than previously reported. This rate of recurrence greatly exceeds that for cutaneous SCCs in general and may be caused by residual postsurgical HPV. (3) The rate of metastasis, however, appears to be low.     

Techniques for cutaneous sutured closures: variants and indications

Many different suture techniques are routinely used by cutaneous surgeons for the closure of surgical wounds. This paper reviews several common suture techniques and their associated subtypes. In particular, for each technique, we discuss the method for placement, generally accepted indications, controversies regarding utility, and objective evidence of efficacy.     

Chronic pain in land mine accident survivors in Cambodia and Kurdistan

The aims of the study were to study chronic pain in land mine accident survivors, and to study the impact of trauma and trauma care parameters on chronic pain. The level of chronic pain was registered (patient-rated and by clinical examination) in 57 severely injured adult land mine accident survivors in Cambodia and Northern Iraq more than one year after the accident. As all study patients had been managed by a standardized trauma system, we could assess the impact of injury severity and primary trauma care on chronic pain. 64% of the study patients (n=36) had chronic pain syndromes (non-significant difference between the two countries). 68% of the amputees (19 out of 28) had phantom limb pain. Pre-injury trauma exposure, the severity of the actual trauma, and the quality of trauma care had no impact on end point chronic pain. In 85% of cases (n=48), the economic standing of the patients' family had deteriorated after the accident. Patient-rated loss of income correlated with the rate of chronic pain syndromes.     

Atypical distant metastases from hypopharyngeal cancer

Hypopharyngeal squamous carcinoma is an aggressive disease with a high frequency of local and distant spread. Distant metastasis is seen more often now because of better loco-regional control due to more aggressive multimodal therapy. This article reports two cases of unusual metastatic disease from squamous carcinoma of pyriform sinus and reviews the metastatic disease in hypopharyngeal squamous cancers. The first was a case of metastatic pericardial effusion and the second was a metastasis to soft tissues of the scapular region and lung.     

Pain associated with injection of botulinum A exotoxin reconstituted using isotonic sodium chloride with and without preservative: a double-blind, randomized controlled trial

CONTEXT: Botulinum A exotoxin is used for various indications, including the treatment of dynamic forehead lines. OBJECTIVE: To determine whether injection with botulinum A exotoxin reconstituted with preservative-containing normal saline (isotonic sodium chloride) is less painful than injection with exotoxin that has been reconstituted with preservative-free saline. DESIGN: Two arms: (1) retrospective study; (2) double-blind, randomized controlled trial. SETTING: A multiple-physician dermatology practice. PATIENTS: (1) Retrospective study-20 consecutive adult patients presenting for treatment of upper-face dynamic lines; (2) prospective study-15 consecutive adult patients presenting for treatment of upper-face dynamic lines. INTERVENTION: In prospective study only, one side (left or right) of the face was treated with exotoxin reconstituted with preservative-containing saline, and the other side, with exotoxin reconstituted with preservative-free saline. MAIN OUTCOME MEASURES: (1) Retrospective study-discomfort at current treatment (with preservative-containing saline) compared with discomfort with most recent prior treatment (with preservative-free saline); (2) prospective study-discomfort on the side treated with preservative-containing saline compared with discomfort on the side treated with preservative-free saline. RESULTS: (1) Retrospective study-18 (90%) of 20 patients reported that treatment with exotoxin reconstituted with preserved saline was less painful than prior treatment with exotoxin reconstituted with preservative-free saline; (2) prospective study-15 (100%) of 15 patients reported less pain in the side of their face treated with exotoxin reconstituted with preservative-containing saline (P<.001). Pain on the preservative-containing side was 54% less. No difference in treatment efficacy between the sides was observed by investigators or patients. CONCLUSION: Use of preservative-containing saline to reconstitute botulinum A exotoxin can significantly decrease patient discomfort on injection.     

Antioxidant enzyme activities and malondialdehyde levels in patients with obsessive-compulsive disorder

To examine the importance of free radicals in the pathogenesis of obsessive-compulsive disorder (OCD), we aimed to evaluate whether malondialdehyde (MDA), a product of lipid peroxidation, and antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] activity levels were associated with OCD. The patients were divided into two subgroups according to whether DSM-IV major depressive disorder (MDD) was accompanied (OCD + MDD) or not (OCD - MDD). The MDA and antioxidant enzyme levels both in patients and controls were determined. SOD activity levels were significantly higher in the OCD + MDD group compared with the control and the OCD - MDD group. Although the OCD - MDD group had slightly higher SOD activity levels as compared with the controls, the difference was not statistically significant. GSH-Px activity levels were statistically significantly higher in both groups compared with controls. Likewise, there was a significant difference in GSH-Px activity levels between the OCD + MDD and OCD - MDD group. CAT activity levels were slightly higher in the OCD + MDD group compared with the OCD - MDD and control group. MDA levels in both groups were significantly higher than in controls. In addition, the difference in MDA levels between both groups was statistically significant. In conclusion, our results suggest that OCD is associated with free radicals and that it may be a heterogeneous subtype including some biological indications of anxiety and affective disorders. More comprehensive and detailed studies are needed to decipher the exact role of free radicals in OCD.