Novel method of intralesional cidofovir injection into laryngotracheal papillomata

Laryngeal papillomatosis is characterised by multiple papillomata affecting the upper respiratory tract. This condition is difficult to treat due to its recurrent nature. Treatment often involves surgical debulking. A number of non-surgical treatments have been reported. Intralesional cidofovir, a cytosine nucleoside analogue with antiviral activity, has been used in an attempt to manage the condition. We present a novel technique of administering cidofovir in a case of recurrent laryngotracheal papillomata.     

Endoluminal reconstruction of the arterial wall with endothelial cell/glue matrix reduces restenosis in an atherosclerotic rabbit

OBJECTIVES: The objectives of this study were 1) to improve the attachment of reimplanted endothelial cells (EC) using a fibrin glue, and 2) to assess the impact of endothelial reseeding on restenosis eight weeks after balloon angioplasty. BACKGROUND: A possible mechanism contributing to restenosis after balloon angioplasty is the loss of the EC lining. Previous attempts to reseed EC had little effect due to rapid loss of the seeded cells. METHODS: Twelve atherosclerotic rabbits were subjected to angioplasty of iliac arteries and reseeding procedure. One iliac artery was subjected to EC/glue reconstruction and a contralateral site to EC seeding without glue. The animals were sacrificed after 4 h. In another series 12 rabbits were treated in the same fashion and were restudied at eight weeks. Additionally, in 10 animals one iliac was subjected to glue treatment, and another served as control. RESULTS: Histological examination demonstrated the ability of this method to reattach the EC/glue matrix circumferentially to 68.0 +/- 6.7% of the arterial wall in comparison with 13.5 +/- 3.9% reattachment after EC seeding. Morphometry at eight weeks showed that the lumen area was significantly greater in the EC/glue group (1.23 +/- 0.35 mm2) than in the EC seeding alone (0.65 +/- 0.02 mm2) and 0.72 +/- 0.41 mm2 in the glue group. This was principally accounted for by the statistically significant differences in the intimal area (0.76 +/- 0.18 mm vs. 1.25 +/-0.26 mm2 and 1.01 +/- 0.53 mm2, respectively). CONCLUSIONS: The attachment of EC after angioplasty can be greatly improved with fibrin glue matrix. The near 70% endothelial coverage achieved by this method resulted in a significant reduction of restenosis in atherosclerotic rabbit.     

Somatic mutation of bcl-6 genes can occur in the absence of V(H) mutations in chronic lymphocytic leukemia

Somatic mutation in immunoglobulin variable (V) region genes occurs largely in the germinal center and, after neoplastic transformation, imprints V genes of B-cell tumors with the mutational history of the cell of origin. Recently, it has been found that chronic lymphocytic leukemia (CLL) consists of 2 subsets, each with a different clinical course, one with unmutated V(H) genes consistent with a naive B cell, and the other with mutated V(H) genes consistent with transit through the germinal center. However, somatic mutation also occurs at another distinct locus, the 5' noncoding region of the bcl-6 gene, in both B-cell tumors and in normal germinal center B cells. To probe the suggestive link between the occurrence of mutations in V(H) and bcl-6 genes, we analyzed the nature of somatic mutation at these distinct loci in the 2 CLL subsets. Unexpectedly, we found no such link in the CLLs defined by unmutated V(H) genes, with 4 of 10 cases clearly showing mutations in bcl-6. In those CLLs defined by somatically mutated V(H) genes, 4 of 9 cases predictively showed bcl-6 mutations. The frequency of bcl-6 mutations was comparable in both subsets, with mutations being biallelic, and in 3 of 8 cases indicative of clonal origins. Surprisingly, intraclonal variation, which is not a feature of V(H) genes in CLL, was found in 6 of 8 cases in both subsets. These data indicate that somatic mutation of the V(H) and bcl-6 loci may not necessarily occur in tandem in CLL, suggesting diverse pathways operating on the 2 genes.     

Sleep disorders in pregnancy

PURPOSE OF REVIEW: Sleep disturbances are frequent during pregnancy. The spectrum of association between pregnancy and sleep disturbances ranges from an increased incidence of insomnia, nocturnal awakenings, and parasomnias (especially restless legs syndrome) to snoring and excessive sleepiness. These disturbances occur as a result of physiologic, hormonal, and physical changes associated with pregnancy. Although the timing and occurrence of different sleep disorders varies, they are most prevalent during the third trimester. Despite reports of the various sleep problems, the exact nature and incidence of sleep disorders in pregnancy is not known. Given that limitation, we are presenting an up-to-date review of the current understanding of the relation between sleep and pregnancy. RECENT FINDINGS: Studies suggest that pregnancy affects sleep in multiple ways. There are hormonal changes, physiologic changes, physical factors, and behavioral changes in a pregnant woman-all of which may affect her sleep. They may affect the duration and quality of sleep and lead to a variety of sleep disorders. Pregnancy may also affect an existing sleep disorder. Particular attention may be given to obese pregnant women who would gain more weight during pregnancy or those who develop hypertensive conditions (eg, preeclampsia). Snoring may be more common in women with preeclampsia and the pressor responses to obstructive respiratory events during sleep may be enhanced in preeclamptic women when compared with those with obstructive sleep apnea alone. Several investigators have suggested that obstructive sleep apnea (OSA) may be common in pregnant women despite the presence of intrinsic mechanisms that seem to be geared towards preventing sleep apnea. However, the exact incidence and prevalence of sleep apnea in pregnant women is uncertain. In addition, it is unclear if criteria that are used to define sleep apnea in the general population should be applied to pregnant women. Further investigations are needed to determine if lower thresholds for management of OSA should be used in pregnant women to prevent harm to the fetus. SUMMARY: In conclusion, sleep disturbances are common during pregnancy though the full extent of this relation remains undefined. Large, multi-center, prospective studies are needed for better understanding.     

A comparison of different balance tests in the prediction of falls in older women with vertebral fractures: a cohort study

BACKGROUND: people with vertebral fractures are at high risk of developing hip fractures. Falls risk is important in the pathogenesis of hip fractures. AIM: to investigate if balance tests, in conjunction with a falls history, can predict falls in older women with vertebral fractures. METHODS: a cohort study of community-dwelling women aged over 60 years, with vertebral fractures. Balance tests investigated were: 5 m-timed-up-and-go-test (5 m-TUG), timed 10 m walk, TURN180 test (number of steps to turn 180 degrees ), tandem walk, ability to stand from chair with arms folded. Leg extensor power was also measured. OUTCOME MEASURE: fallers (at least one fall in a 12 month follow-up period) versus non-fallers. RESULTS: one hundred and four women aged 63-91 years [mean=78 +/- 7], were recruited. Eighty-six (83%) completed the study. Four variables were significantly associated with fallers: previous recurrent faller (2+ falls) [OR=6.52; 95% CI=1.69-25.22], 5 m-TUG test [OR=1.03; 1.00-1.06], timed 10 m walk [OR=1.07; 1.01-1.13] and the TURN180 test [OR=1.22; 1.00-1.49] [P <0.05]. Multi-variable analysis showed that only two variables, previous recurrent faller [OR=5.60; 1.40-22.45] and the 5 m-TUG test [OR=1.04; 1.00-1.08], were independently significantly associated with fallers. The optimal cut-off time for performing the 5 m-TUG test in predicting fallers was 30 s (area under ROC=60%). Combining previous recurrent faller with the 5 m-TUG improved prediction of fallers [OR=16.79, specificity=100%, sensitivity=13%]. CONCLUSIONS: a previous history of recurrent falls and the inability to perform the 5 m-TUG test within 30 s predicted falls in older women with vertebral fractures. Combining these two measures can predict fallers with a high degree of specificity (although a low sensitivity), allowing the identification of a group of patients suitable for fall and fracture prevention measures.     

Relationship between the cardiometabolic syndrome and obstructive sleep apnea

Obstructive sleep apnea (OSA), characterized by cessation of air flow for a minimum of 10 seconds despite continuous respiratory effort, is a prevalent condition in our society. Recent studies demonstrate that OSA is an independent risk factor for insulin resistance and the cardiometabolic syndrome. Hypoxemia and sleep fragmentation from OSA appear to produce autonomic activation, alterations in neuroendocrine function, and increased amounts of inflammatory cytokines (interleukin 6 and tumor necrosis factor alpha). These variables have important roles in the pathogenesis of insulin resistance and the cardiometabolic syndrome. It can be concluded that insulin sensitivity, a key contributor to the pathogenesis of the cardiometabolic syndrome, is mainly determined by the extent of obesity and, to a lesser extent, by OSA. The authors review OSA and summarize recent discoveries and proposed mechanisms of the causal relationship that OSA has with insulin resistance and the cardiometabolic syndrome independent of many confounding comorbidities.