Cryotherapy for treatment of oral lesions

Cryotherapy is the deliberate destruction of tissue by application of extreme cold. It is well received by patients due to a relative lack of discomfort, the absence of bleeding and minimal to no scarring after healing. It has many applications in oral medicine and clinical oral pathology, and is extremely usefu in patients for whom surgery is contra-indicated due to either age or medical history. In this paper we outline the principles, mechanisms of action, and current applications of cryotherapy in the treatment of oral lesions, and present some clinical cases.     

Resequencing of the characterised CTGF gene to identify novel or known variants, and analysis of their association with diabetic nephropathy

Connective tissue growth factor (CTGF) has been implicated in the pathogenesis of diabetic nephropathy; however, to date there have been no reports of genomic analysis on this gene. The CTGF gene was comprehensively screened using WAVE (dHPLC) technology and direct capillary sequencing. Single nucleotide polymorphisms (SNPs) with minor allele frequencies greater than 5% were further investigated in an Irish, type 1 diabetic population. The case-control collection consisted of 272 diabetics with nephropathy and 367 non-nephropathic diabetic controls who were genotyped using TaqMan and Pyrosequencing technologies. Ten SNPs were identified, of which seven were novel. Four SNPs are located in the promoter, one in exon 2, two in intron 2 and three in the 3 untranslated region. Based on in silico analysis, three SNPs, c.–650G>C, c.–484T>C and c.247G>C, are potentially functional. Subsequent statistical analysis for common SNPs, c.–650G>C, c.–420InsT, c.–220G>C, c.289+94T>C and c.289+98T>C, in the case-control study revealed no significant differences in genotype or allele frequencies. CTGF has emerged as a biological candidate gene for diabetic nephropathy; however, no significant association was detected between common CTGF SNPs and nephropathy in this population.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2

Hepatic steatosis is a core feature of the metabolic syndrome and type 2 diabetes and leads to hepatic insulin resistance. Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2), is a key regulator of both mitochondrial fatty acid oxidation and fat synthesis. We used a diet-induced rat model of nonalcoholic fatty liver disease (NAFLD) and hepatic insulin resistance to explore the impact of suppressing Acc1, Acc2, or both Acc1 and Acc2 on hepatic lipid levels and insulin sensitivity. While suppression of Acc1 or Acc2 expression with antisense oligonucleotides (ASOs) increased fat oxidation in rat hepatocytes, suppression of both enzymes with a single ASO was significantly more effective in promoting fat oxidation. Suppression of Acc1 also inhibited lipogenesis whereas Acc2 reduction had no effect on lipogenesis. In rats with NAFLD, suppression of both enzymes with a single ASO was required to significantly reduce hepatic malonyl-CoA levels in vivo, lower hepatic lipids (long-chain acyl-CoAs, diacylglycerol, and triglycerides), and improve hepatic insulin sensitivity. Plasma ketones were significantly elevated compared with controls in the fed state but not in the fasting state, indicating that lowering Acc1 and -2 expression increases hepatic fat oxidation specifically in the fed state. These studies suggest that pharmacological inhibition of Acc1 and -2 may be a novel approach in the treatment of NAFLD and hepatic insulin resistance.     

Total synthesis of 2‴,5‴-diepisilvestrol and its c1‴ epimer: key structure activity relationships at c1‴ and c2‴

The first total synthesis of the low-abundance natural product 2?,5?-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta[b]benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2?,5?-diepisilvestrol (4) and its C1 epimer 1?,2?,5?-triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2?,5?-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1?,2?,5?-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1? and C2? has a large effect on the biological activity.     

Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000–2009

Background:

Post-molar pregnancy gestational trophoblastic tumours (GTT) have been curable with chemotherapy treatment for over 50 years. Because of the rarity of the diagnosis, detailed structured information on prognosis, treatment escalations and outcome is limited.

Methods:

We have reviewed the demographics, prognostic variables, treatment course and clinical outcomes for the post-mole GTT patients treated at Charing Cross Hospital between 2000 and 2009.

Results:

Of the 618 women studied, 547 had a diagnosis of complete mole, 13 complete mole with a twin conception and 58 partial moles. At the commencement of treatment, 94% of patients were in the FIGO low-risk group (score 0–6). For patients treated with single-agent methotrexate, the primary cure rate ranged from 75% for a FIGO score of 0–1 through to 31% for those with a FIGO score of 6.

Conclusion:

In the setting of a formal follow-up programme, the expected cure rate for GTT after a molar pregnancy should be 100%. Prompt treatment and diagnosis should limit the exposure of most patients to combination chemotherapy. Because of the post-treatment relapse rate of 3% post-chemotherapy, hCG monitoring should be performed routinely.     

Factors influencing visibility and diagnostic yield of transbronchial biopsy using endobronchial ultrasound in peripheral pulmonary lesions

Background and objective:   Endobronchial ultrasound (EBUS) has increased the diagnostic yield of bronchoscopic biopsy of peripheral pulmonary lesions (PPL). However, certain lesions cannot be localized by EBUS, and the factors associated with the visibility of PPL by EBUS have not been investigated. This study evaluated the factors predicting the visualization of EBUS in PPL and the diagnostic yield of EBUS-guided transbronchial biopsy (TBB).
Methods:   n 2007, 83 patients with PPL underwent EBUS-guided TBB, and their medical records were reviewed and analysed retrospectively.
Results:   Of the 83 patients examined, EBUS images could not be obtained in 23 patients (28%). Lesion size was a determining factor for the visibility of PPL, with the visualization yield of EBUS in lesions <20 mm being significantly lower than that in lesions ≥20 mm ( P  < 0.001). A definitive diagnosis of PPL localized by EBUS was established using EBUS-guided TBB in 73% of patients. There were no significant differences in diagnostic yield related to underlying disease, lobar distribution, CT scan appearance or presence of complications. Multivariate analysis revealed that the location of PPL on CT scans and position of the probe were independent predictors of the diagnostic yield by EBUS-guided TBB ( P  < 0.001 and P  = 0.001, respectively).
Conclusions:   Lesion size is a significant factor predicting visualization of EBUS for PPL. The location of PPL on CT scans and position of the probe are significantly related to a higher diagnostic yield with EBUS-guided TBB.     

Psychiatric Comorbidity and Other Psychological Factors in Patients with “Chronic Lyme Disease”

Background

There is no evidence of current or previous Borrelia burgdorferi infection in most patients evaluated at university-based Lyme disease referral centers. Instead, psychological factors likely exacerbate the persistent diffuse symptoms or “Chronic Multisymptom Illness” (CMI) incorrectly ascribed to an ongoing chronic infection with B. burgdorferi. The objective of this study was to assess the medical and psychiatric status of such patients and compare these findings to those from patients without CMI.

Methods

There were 240 consecutive patients who underwent medical evaluation and were screened for clinical disorders (eg, depression and anxiety) with diagnoses confirmed by structured clinical interviews at an academic Lyme disease referral center in New Jersey. Personality disorders, catastrophizing, and negative and positive affect also were evaluated, and all factors were compared between groups and with functional outcomes.

Results

Of our sample, 60.4% had symptoms that could not be explained by current Lyme disease or another medical condition other than CMI. After adjusting for age and sex, clinical disorders were more common in CMI than in the comparison group (P <.001, odds ratio 3.54, 95% confidence interval, 1.97-6.55), but personality disorders were not significantly more common. CMI patients had higher negative affect, lower positive affect, and a greater tendency to catastrophize pain (P <.001) than did the comparison group. Except for personality disorders, all psychological factors were related to worse functioning. Our explanatory model based on these factors was confirmed.

Conclusions

Psychiatric comorbidity and other psychological factors are prominent in the presentation and outcome of some patients who inaccurately ascribe longstanding symptoms to “chronic Lyme disease.”