Associations between physical and mental health problems and sexual dysfunctions in sexually active Danes

IntroductionStudies have shown a high prevalence of sexual dysfunctions among individuals with a variety of health problems.AimTo obtain a population‐based assessment of these matters, we studied associations between indicators of physical and mental health problems and sexual dysfunctions in Denmark.MethodsWe used questionnaire data from 4,415 sexually active men (mean age 48 years) and women (mean age 45 years) who participated in a nationally representative survey in 2005. Cross‐sectional associations of overall health and physical and mental health problems with sexual dysfunctions in the last year were estimated by logistic regression‐derived, confounder‐adjusted odds ratios (OR_adj).Main Outcome MeasuresWe calculated OR_adj with 95% confidence intervals (CI) for erectile dysfunction, anorgasmia, premature ejaculation, and dyspareunia in men, for lubrication insufficiency, anorgasmia, dyspareunia, and vaginismus in women, and for sexual dysfunction and sexual difficulties overall in both sexes.ResultsSexual dysfunction was significantly more common among participants with poor self‐rated health (OR_adj 1.86, 95% CI 1.05‐3.33 in men, OR_adj 1.91, 1.08–3.37 in women). Physical health problems were significantly associated with male sexual dysfunctions (OR_adj 1.75, 1.18–2.61), whereas mental health problems were significantly associated with female sexual dysfunctions (OR_adj 2.59, 1.60–4.22).ConclusionAmong sexually active Danes, poor self‐reported overall health is associated with increased rates of sexual dysfunction in both sexes, with physical health problems mainly affecting men's sex lives, and mental health problems being strongly associated with female sexual dysfunction. Christensen BS, Grønbæk M, Osler M, Pedersen BV, Graugaard C, and Frisch M. Associations between physical and mental health problems and sexual dysfunctions in sexually active Danes. J Sex Med 2011;8:1890–1902.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Efficient replication of full-length murine leukemia viruses modified at the dimer initiation site regions

Retroviruses encapsidate two copies of full-length viral RNA molecules linked together as a dimeric genome. RNA stem loop structures harboring palindromic (or "kissing") loop sequences constitute important cis-elements for viral dimerization known as dimer initiation sites (DIS). In murine leukemia virus (MLV), a 10-mer and a 16-mer palindrome (DIS-1 and DIS-2, respectively) located in the viral leader region mediate dimerization in vitro and affect dimer stability of vector RNA in vivo. We have investigated the effect on viral replication of introducing deletions or nucleotide substitutions within these palindromes in a full-length MLV genome. Our results demonstrate that viruses modified at the dimer initiation site regions are viable and show wild-type levels of RNA encapsidation. One mutant lacking the DIS-1 palindrome was severely impaired and displayed an increased cellular ratio of spliced versus genomic RNA that most likely contributes to the inefficient replication. The implications for development of DIS-modified retrovirus-based vectors are discussed.     

Computer-assisted prenatal aneuploidy screening for chromosome 13, 18, 21, X and Y based on multiplex ligation-dependent probe amplification (MLPA)

In routine prenatal diagnostics we used a commercial multiplex ligation-dependent probe amplification (MLPA) kit for aneuploidy screening for chromosomes 13, 18, 21, X and Y. We present the results of 1593 consecutive prenatal samples analysed and diagnosed prior to knowledge of the G-banding analysis during 8-month routine use of computer-assisted MLPA aneuploidy screening. In total, 27 aneuploidies were detected. There were no false positive results while two false negative results could be explained by a placental mosaicism and a partial monosomy, respectively. In total, 3.2% of the samples were inconclusive. We conclude that automatic computer assisted MLPA is a rapid, simple and reliable method for detection of aneuploidies in prenatal diagnostics.     

Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens

The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.     

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

Skeletal consequences of familial hypocalciuric hypercalcaemia vs. primary hyperparathyroidism

Objectives Bone metabolism is only superficially described in familiar hypocalciuric hypercalcaemia (FHH). We describe and compare biochemical and osteodensitometric variables in FHH and primary hyperparathyroidism (PHPT) and assess whether they can improve the diagnostic discrimination between the groups. Design Cross‐sectional. Patients Sixty‐six FHH patients with known calcium‐sensing receptor (CASR) gene mutations and 147 PHPT patients. Measurements We determined calcium, creatinine, phosphate, magnesium, parathyroid hormone (PTH), 25OHD, 1,25(OH)₂D and alkaline phosphatase (AP) in plasma, NTx/creatinine ratio in urine and calculated the calcium/creatinine clearance ratio (CCCR). We performed dual energy X‐ray absorptiometry at the lumbar spine, hip, forearm and whole body. Results When compared with normal controls, the FHH patients had increased levels of PTH and AP with normal U‐NTx and regional Z‐scores. Increased phenotypic expression of CASR mutations in terms of hypercalcaemia was associated with higher lumbar spine bone mineral density, but not with bone markers. FHH were younger and leaner than the PHPT patients. They had comparable plasma Ca²⁺ and 25OHD, but lower levels of PTH, 1,25(OH)₂D, AP and U‐NTx. They had higher Z‐scores in the hip and in the forearm. We achieved the best discrimination between groups by multiplying CCCR with AP, 1,25(OH)₂D and PTH, but the difference between the area under the curves by receiver operating characteristic analysis remained insignificant. Conclusion Familiar hypocalciuric hypercalcaemia is associated with increased PTH and AP compared to normal controls, but not with bone loss irrespective of the severity of the CASR mutations. A multiplicative model including CCCR, AP, 1,25(OH)₂D and PTH insignificantly improved the power of the CCCR to differentiate between FHH and PHPT. However, we still recommend CASR gene analysis in patients with a CCCR <0·020.     

Abnormal Papanicolaou smear. A population-based study of risk factors in Greenlandic and Danish women

Possible risk factors for abnormal Papanicolaou smear were investigated in a population-based cross-sectional study. From Nuuk (Greenland) and Nyk?bing Falster (Denmark), random samples of 800 women aged 20-39 years were drawn. Totals of 586 and 661 women were included in Greenland and Denmark, respectively. All women went through a personal interview, and had a gynecologic examination including a PAP smear and cervical swab for HPV analysis. A blood sample was taken for analysis of HSV type specific antibodies. Multiple sexual partners was the most important risk factor for abnormal cervical cytology (OR = 4.2). An infectious etiology was also indirectly supported by a relatively protective effect of barrier contraceptive methods (OR = 0.6). The simultaneous finding of HPV 16/18 as a significant risk factor (OR = 2.4) cannot be taken uncritically as support for a causal effect of this HPV type, since such a relationship between cytological changes of the cervix and HPV infection could also emerge if the positive PAP smear was not just a measure of intra-epithelial neoplasia but also an expression of the infection itself on the cervix.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.