Echocardiographic assessment at rest and during stress in patients with intermittent claudication

Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n?=?111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.

Trial registration: ClinicalTrials.gov identifier: NCT01219842.     

Deep sequencing detects human papillomavirus (HPV) in cervical cancers negative for HPV by PCR

Background Human papillomavirus (HPV) is a necessary cause of cervical cancer, although some invasive cervical cancers may test negative by HPV PCR. We previously requested all invasive cervical cancers in Sweden during 10 years and subjected them to PCR. We also optimised methods for deep sequencing of formalin-fixed paraffin-embedded samples.Methods Using Novaseq 6000, we simultaneously sequenced total DNA and cDNA from 392 HPV PCR-negative cervical cancers. Non-human reads were queried against all known HPVs. The complete database now contains PCR and/or deep sequencing data on 2850 invasive cervical cancers.Results HPV sequences were detected in 169/392 of HPV PCR-negative cervical cancers. Overall, 30 different HPV types were detected, but only 5 types were present in proportions above 3% of cancers. More than 92% of tumours were HPV-positive in PCR and/or sequencing (95% confidence interval: 91.1–93.1%). Exploring possible reasons for failure to previously detect HPV suggest that more sensitive type-specific PCRs for HPV 31, 33, 45 and 73 targeting retained regions of HPV would have detected most of these (117/392).Conclusions Unbiased deep sequencing provides comprehensive data on HPV types in cervical cancers and appears to be an important tool for quality assurance of HPV screening.Subject terms: Infectious-disease diagnostics, Viral infection, Cervical cancer     

Intermittent catheterization with single- or multiple-reuse catheters: clinical study on safety and impact on quality of life

International Urology and Nephrology - Intermittent catheterization (IC) is a proven effective long-term bladder management strategy for individuals who have lower urinary tract dysfunction. This...     

Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma

PurposeMore than half of the familial cutaneous melanomas have unknown genetic predisposition. This study aims at characterizing a novel melanoma susceptibility gene.MethodsWe performed exome and targeted sequencing in melanoma-prone families without any known melanoma susceptibility genes. We analyzed the expression of candidate gene DENND5A in melanoma samples in relation to pigmentation and UV signature. Functional studies were carried out using microscopic approaches and zebrafish model.ResultsWe identified a novel DENND5A truncating variant that segregated with melanoma in a Swedish family and 2 additional rare DENND5A variants, 1 of which segregated with the disease in an American family. We found that DENND5A is significantly enriched in pigmented melanoma tissue. Our functional studies show that loss of DENND5A function leads to decrease in melanin content in vitro and pigmentation defects in vivo. Mechanistically, harboring the truncating variant or being suppressed leads to DENND5A losing its interaction with SNX1 and its ability to transport the SNX1-associated vesicles from melanosomes. Consequently, untethered SNX1-premelanosome protein and redundant tyrosinase are redirected to lysosomal degradation by default, causing decrease in melanin content.ConclusionOur findings provide evidence of a physiological role of DENND5A in the skin context and link its variants to melanoma susceptibility.     

Optimal dosage of chlorhexidine acetate in chewing gum

Abstract. In a previous study, 800 mg pieces of sorbitol-flavored gum, each piece containing 5 mg chlorhexidine (CHX) acetate, when chewed 2 at the time 5 × daily, were found to have an excellent plaque growth inhibiting effect. The aim of Trial 1 of the present study was to assess whether chewing only 2 × daily, 2 pieces of the same concentration CHX gum for about 10 min would be as effective. 6 dental students participated in the 3 × randomly crossed over double-blind clinical trial. During the 5-day chewing periods, no other oral hygiene measures were allowed. The Hibitane Dental (HD) rinse was used as a positive and the gum base containing neither CHX nor the sweetening agent as a negative control. At the end of each test period, recordings were made for the plaque index (P1I), the plaque wet weight (PWW) and the relative area of plaque covered tooth surface (plaque area %). Chewing of CHX gum twice daily inhibited plaque growth as effectively as the HD rinse. The aim of Trial 2 was to assess the antiplaque effect of lower concentration CHX gums with, hopefully, a less unpleasant taste. For this trial, 8 dental students were recruited to chew 2 × daily during 6-day periods two 800 mg pieces of sorbitol-flavored gum, each piece now containing either 5 mg, 4 mg or 3 mg CHX acetate. The effect of these dosages did not differ from the effect of the HD rinse. Chewing 2 × daily for 6 days only one 800 mg piece of gum containing 5 mg CHX acetate resulted in higher P1I and plaque area % scores than use of HD rinses 2 × daily. The subjective evaluation by the test subjects revealed an inverse correlation between effect and taste of the CHX products.     

Pulsed radiofrequency in the treatment of persistent pain after inguinal herniotomy: a systematic review

In the United States, it is estimated that between 6000 and 18,000 individuals each year present with disabling pain after inguinal hernia repair. Although surgical treatment with mesh removal is one of few options available, effective alternatives to nonsurgical management are needed. The use of pulsed radiofrequency (PFR), leading to nondestructive lesions of nerve structures, has been proposed as a treatment option. To examine the evidence of treatment efficacy, a systematic literature search was made. From the databases PubMed, Embase, and CINAHL, 4 case reports were retrieved and 8 patients were included for analysis. The PFR treatment was peripheral (n = 4) and central (n = 4). Pain relief varied between 63% and 100%, the follow-up period was 3 to 9 months, and no adverse effects or complications were reported. In conclusion, the evidence base of PRF in persistent pain after inguinal herniotomy is fairly limited. Suggestions for improved research strategies are presented.     

Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution

Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin γ-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.