Proximal Esophageal Contractions in Laryngectomized Patients

After laryngectomy for treatment of laryngeal cancer, the distal esophageal contractions have low amplitude. Our hypothesis is that proximal esophageal contractions are also impaired. We studied the proximal esophageal contractions in 20 laryngectomized patients (16 men) with a mean age of 44.2 years, 12 rehabilitated patients with esophageal speech, and 12 controls (7 men, mean age of 46.5 years). We used the manometric method with continuous perfusion. All subjects were studied in the sitting position and performed five swallows of a 5-ml bolus of water alternated with five dry swallows. The contractions were measured 2 cm below the high-pressure zone of the pharyngoesophageal transition. The results showed that the amplitude and duration of contractions were different in laryngectomized patients compared with controls. The amplitude of contractions of patients (wet swallows: 37.3 ± 20.7 mmHg, mean ± SD) was lower than that of controls (81.1 ± 31.7 mmHg). The duration of contractions was also lower in laryngectomized patients (2.2 ± 0.7 s) than in controls (2.6 ± 0.6 s). We conclude that the proximal esophageal contraction amplitude and duration of laryngectomized patients are lower than controls, a fact suggesting that laryngectomy may affect the proximal esophageal contractions.     

Alpha‐melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus‐like model

Alpha‐melanocyte stimulating hormone (α‐MSH) is a neuropeptide exhibiting anti‐inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α‐MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α‐MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α‐MSH analogue [Nle4, DPhe7]‐α‐MSH (NDP–MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti‐nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α‐smooth muscle actin (α‐SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin‐releasing factor (CRF) and α‐MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)‐6, IL‐10, proteinuria and mesangial cell proliferation together with glomerular expression of α‐SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP‐MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP–MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α‐SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α‐MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.     

p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital adrenal hyperplasia patients

More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21-hydroxylase gene (CYP21A2) mutations. The CYP21A2 gene is located in the human leukocyte antigen (HLA) class III region on the short arm of chromosome 6p21.3, along with an inactive pseudogene, CYP21A1P, that is 98% homologous in its coding sequence with CYP21A2. Most CYP21A2 mutations result from intergenic recombinations between CYP21A2 and the closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for only 5% to 10% of 21-hydroxylase deficiency alleles. However, detection of these rare and spontaneous mutations has continued to expand worldwide. We identified 2 novel CYP21A2 missense mutations (p.H282N and p.Y191H) in 2 Italian patients with simple-virilizing and nonclassic CAH forms. Functional analysis of these CYP21A2 mutations was performed. Functional in vitro assay for mutagenized CYP21A2 enzymes was performed in transiently transfected mammalian cells to test the residual enzyme activity and the apparent kinetic values. The residual activities obtained allowed us to classify the p.H282N and p.Y191H variants as simple-virilizing and nonclassic CAH associated mutations, respectively. These results correlate with the rate of severity of the patients' disease. This finding provides a further contribution for assisting in the diagnosis of CAH patients.     

Elevated plasma levels and platelet-associated expression of the pro-thrombotic and pro-inflammatory protein, TNFSF14 (LIGHT), in sickle cell disease

Chronic vascular inflammation and endothelial activation may initiate vaso‐occlusion in sickle cell disease (SCD). TNFSF14 (CD258; LIGHT), a recently‐identified pro‐thrombotic and pro‐inflammatory tumour necrosis factor (TNF)‐superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet‐free plasma from healthy‐control individuals (CON), steady‐state sickle cell anaemia (SCA), SCA on hydroxycarbamide therapy (SCAHC) and haemoglobin SC (HbSC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and HbSC, compared to CON individuals. In SCA/SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers (CD40LG , IL8 and ICAM1). Platelet‐membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (≥2·5 m/s) in a population of SCA/SCAHC patients. The pro‐inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target.     

HPV and precancerous lesions of anal canal in women: systematic review

Objective  

The infection caused by human papillomavirus (HPV) in the anogenital area is considered the most common sexually transmitted infection in the world. Although anal cancer is relatively uncommon in the general population, there has been a significant increase in incidence in recent years. In this review, we focused on research on anal lesions in women.     

Comparison of the effects of continuous positive airway pressure,oral appliance and exercise training in obstructive sleep apnea syndrome

OBJECTIVE:

There are several treatments for obstructive sleep apnea syndrome, such as weight loss, use of an oral appliance and continuous positive airway pressure, that can be used to reduce the signs and symptoms of obstructive sleep apnea syndrome. Few studies have evaluated the effectiveness of a physical training program compared with other treatments. The aim of this study was to assess the effects of physical exercise on subjective and objective sleep parameters, quality of life and mood in obstructive sleep apnea patients and to compare these effects with the effects of continuous positive airway pressure and oral appliance treatments.

METHODS:

Male patients with moderate to severe obstructive sleep apnea and body mass indices less than 30 kg/m2 were randomly assigned to three groups: continuous positive airway pressure (n = 9), oral appliance (n = 9) and physical exercise (n = 7). Polysomnographic recordings, blood samples and daytime sleepiness measurements were obtained prior to and after two months of physical exercise or treatment with continuous positive airway pressure or an oral appliance. Clinicaltrials.gov: NCT01289392

RESULTS:

After treatment with continuous positive airway pressure or an oral appliance, the patients presented with a significant reduction in the apnea-hypopnea index. We did not observe changes in the sleep parameters studied in the physical exercise group. However, this group presented reductions in the following parameters: T leukocytes, very-low-density lipoprotein and triglycerides. Two months of exercise training also had a positive impact on subjective daytime sleepiness.

CONCLUSIONS:

Our results suggest that isolated physical exercise training was able to modify only subjective daytime sleepiness and some blood measures. Continuous positive airway pressure and oral appliances modified the apnea-hypopnea index.     

Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

OBJECTIVES:

To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleate

METHODS:

A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer''s test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872

RESULTS:

All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer''s test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression.

CONCLUSIONS:

All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface after three months of glaucoma treatment.