Dyspareunia: a difficult symptom in gynaecological practice

Dyspareunia is recurrent or persistent genital pain associated with sexual intercourse. It is a symptom that can have a significant impact on women's health, relationships and quality of life. There are multiple different causes for it, including both organic and psychosexual components. Despite the high prevalence of sexual pain, estimated to between 3 and 18% worldwide, few guidelines exist for its evaluation and management. Adequate assessment requires a comprehensive sexual history, a systematic and thorough examination of the lower genital tract to rule out anatomical causes and an exploration of potential psychosexual causes. Further investigations may include swabs and a pelvic ultrasound scan. In some cases a diagnostic laparoscopy may be required if there is evidence of endometriosis or utero-vaginal pathology that does not respond to conservative management. This article considers the diagnosis and investigation of women complaining of dyspareunia.     

Neuroanatomical Correlates of Skin Conductance Orienting in Normal Humans: A Magnetic Resonance Imaging Study

Although little is known about the neuroanatomical basis of skin conductance orienting in intact normal humans, the limited literature on animals and humans with neurological and clinical disorders implicate prefrontal, temporal/amygdala, and pons brain areas in mediating skin conductance orienting. This study relates area of these structures using magnetic resonance imaging techniques to skin conductance orienting responses in 17 normal humans in order to test hypotheses that larger area of these excitatory structures will be associated with more orienting responses. Left and right hand skin conductance orienting was significantly associated with left and right prefrontal area (r = .44-.60), area of the pons (r = .43-.54), and left but not right temporal/amygdala area (r = .47-.53). No relationships were observed with areas thought to be unrelated to skin conductance activity (cerebellum, nonfrontal cortical area), medial prefrontal cortex, or the third ventricle. This appears to be the first study relating brain structure to skin conductance orienting in intact normal humans. Although preliminary at the present time, these results implicate prefrontal, pons, and temporal/amygdala areas in the mediation of skin conductance orienting in normal humans.     

Genetic association to the amyloid plaque associated protein gene COL25A1 in Alzheimer's disease

The COL25A1 gene, located in 4q25, encodes the CLAC protein, which has been implicated in Alzheimer's disease (AD) pathogenesis. CLAC was originally identified in amyloid preparations from AD brain and has been shown to be associated with amyloid plaques, inhibition of Abeta-fibril elongation and increased protease resistance of Abeta-fibrils through direct binding to Abeta. These biochemical data as well as the genomic location of the COL25A1 gene in chromosome 4q25 where we previously have reported a weak linkage-signal in Swedish AD families encouraged us to perform a case-control association study of two LD blocks in COL25A1 using 817 AD cases and 364 controls. The LD blocks cover a putative Abeta-binding motif and the variable 3' end of the gene. The analyses indicated association to three of eight analysed SNPs. We found further support for the association by replication in a Swedish population-based longitudinal sample set (n=926). Thus, in addition to the biochemical data, there is now genetic evidence of association between COL25A1 and risk for Alzheimer's disease.     

FISH characterization of head and neck carcinomas reveals that amplification of band 11q13 is associated with deletion of distal 11q

In order to characterize homogeneously staining regions (HSR) and other 11q13 rearrangements identified cytogenetically, we performed fluorescence in situ hybridization (FISH) using a CCND1cosmid and five YAC clones spanning chromosomal bands 11q13–14 on metaphase cells from 14 primary and one metastatic head and neck carcinomas. At the cytogenetic level, a total of 17 HSR were detected in ten cases: five were in derivative chromosomes 11 in band 11q13, and 12 were located in other derivative chromosomes. Other forms of 11q13 rearrangements were observed in five cases, whereas two cases had normal chromosomes 11. FISH analysis demonstrated that all HSR but two were derived from the 11q13 band. The size of the amplicon varied from case to case, but the amplification always included the region covered by YAC 55G7, which contains the CCND1 locus. The amplification of CCND1was confirmed by use of a CCND1cosmid. We also showed that most of the cases (9 of 11) with 11q13 amplification had lost material from distal 11q. The breakpoints were mapped by FISH and were shown to cluster to the region between YACs 55G7 and 749G2. We conclude that loss of gene(s) in distal 11q may be as important as amplification of genes in 11q13 for the biological aggressiveness of head and neck carcinomas. Genes Chromosomes Cancer 22:312–320, 1998. © 1998 Wiley-Liss, Inc.     

Development of a biochemical marker to detect current breast milk intake

The WHO recommends exclusive breastfeeding for 6 months, but despite interventions, breastfeeding rates remain stubbornly low. Financial voucher incentives have shown promise but require a biomarker for validation of intake. This study aimed to develop a simple biochemical assay of infant urine that would tell if an infant was receiving any breast milk to validate maternal report. Urine samples were collected and snap frozen from 34 infants attending with minor illness or feeding problems, of whom 12 infants were exclusively breastfed, nine exclusively formula fed, and 11 mixed breast/formula fed. High‐performance anion exchange chromatography was used to identify discriminating patterns of monosaccharide composition of unconjugated glycans in a sequence of three experiments. The absolute concentration of all human milk oligosaccharides measured blind could detect “any breastfeeding” only with a sensitivity of 48% and specificity of 78%. Unblinded examination of N‐acetylglucosamine (GlcNAc) measured as GlcNH₂ after hydrolysis of GlcNAc improved sensitivity to 75% at the expense of a specificity of 28%. Estimation of the relative abundance of GlcNH2 (GlcNH2[%]) or the ratio of GlcNH2 to endogenous mannose (Man) improved accuracy. In a further blind experiment, the GlcNH2/Man ratio with a cut‐off of 1.5 correctly identified all those receiving “any breast milk,” while excluding exclusively formula fed infants. The GlcNH2/Man ratio in infant urine is a promising test to provide biochemical confirmation of any breastfeeding for trials of breastfeeding promotion.     

Immunohistochemical detection of bcl-2 protein in normal and pathological human liver.

The bcl-2 protein, which prolongs cell survival by blocking apoptosis, is expressed by progenitor cells in several self-renewing tissues and by tumoral cells in some extrahepatic neoplasms. Because the liver is a slow self-renewing tissue, an immunohistochemical study of the cellular distribution of the bcl-2 protein was performed in normal liver (12 cases), nontumoral hepatic lesions (33 cases), and benign or malignant liver tumors (46 cases). In normal liver, bcl-2 was expressed by bile ductules and small bile duct epithelium, but not by hepatocytes or large bile duct epithelium. In cirrhosis and focal nodular hyperplasia, epithelial cells of the ductular proliferation were bcl-2-positive. Eight of 11 cholangiocarcinomas stained positively for bcl-2, whereas all 15 hepatocellular carcinomas were bcl-2-negative. bcl-2 was also expressed in 6 of 14 metastatic adenocarcinomas. These findings suggest that the ductular cells and small bile duct epithelial cells might have a prolonged survival and might be hepatic progenitor cells. In addition, the bcl-2 protein appears to be a marker of cholangiocarcinoma but not of hepatocellular carcinoma and could help in distinguishing between these two primary liver tumors.     

An HLA-DRB α-helix motif shared by DR11 and DR8 alleles is implicated in the pluriallelic restriction of peptide-specific T-cell lines

The T-cell recognition of HLA-DR-peptide complexes is generally restricted by the polymorphism of the DRB molecules but pluriallelic restriction has been described. The molecular basis of restriction and promiscuity of such peptide-specific responses is poorly understood. We isolated a panel of T-cell lines specific for the tetanus toxin peptide p2 (TT830-843) exhibiting pluriallelic restriction by DR11 and DR8 alleles. Fine restriction specificity of the T-cell lines was examined in functional assays against DR oligotyped APCs expressing different variants of DR11 and DR8 alleles. Our results show that (a) polymorphisms between serologically related alleles are relevant in terms of restriction of the peptide-specific T-cell response; in some instances, a single amino acid substitution can determine the restriction of a T-cell line; (b) different patterns of restriction are not the result of specific differences in DR-p2 binding as p2 peptide binds to all DR11 and DR8 alleles tested (DRB1^* 1101, -1102, -1103, -1104, 110X, -0801, -0802, -0803, and -0806); and (c) pluriallelic restriction of the peptide-specific T-cell responses correlates with the presence of a DRB1 α-helix motif (67-71-86) shared by some DR11 and DR8 alleles. Possible implications of pluriallelic restriction of peptide-specific T-cell response in autoimmune disorders associated with DR11 and DR8 are discussed.     

Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum

Objective

To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum.

Methods

We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients' medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients' responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as “patient-regimens.” Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed.

Results

We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a progression-free survival duration of at least 6 months. Patient-regimens involving ER +/PR + disease produced a longer median TTP (8.9 months) than patient-regimens involving ER +/PR − disease did (6.2 months; p = 0.053). This difference approached but did not reach statistical significance.

Conclusions

Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.     

"Expectant Parents": Study protocol of a longitudinal study concerning prenatal (risk) factors and postnatal infant development, parenting, and parent-infant relationships

ABSTRACT: BACKGROUND: While the importance of the infant-parent relationship from the child's perspective is acknowledged worldwide, there is still a lack of knowledge about predictors and long-term benefits or consequences of the quality of parent-infant relationships from the parent's perspective. The purpose of this prospective study is to investigate the quality of parent-infant relationships from parents' perspectives, both in the prenatal and postpartum period. This study therefore focuses on prenatal (risk) factors that may influence the quality of pre- and postnatal bonding, the transition to parenthood, and bonding as a process within families with young children. In contrast to most research concerning pregnancy and infant development, not only the roles and experiences of mothers during pregnancy and the first two years of infants' lives are studied, but also those of fathers. Methods/design The present study is a prospective longitudinal cohort study, in which pregnant women (N = 466) and their partners (N = 319) are followed from 15 weeks gestation until their child is 24 months old. During pregnancy, midwives register the presence of prenatal risk factors and provide obstetric information after the child's birth. Parental characteristics are investigated using self- report questionnaires at 15, 26, and 36 weeks gestational age and at four, six, 12, and 24 months postpartum. At 26 weeks of pregnancy and at six months postpartum, parents are interviewed concerning their representations of the (unborn) child. At six months postpartum, the mother-child interaction is observed in several situations within the home setting. When children are four, six, 12, and 24 months old, parents also complete questionnaires concerning the child's (social-emotional) development and the parent-child relationship. Additionally, at 12 months information about the child's physical development and well-being during the first year of life is retrieved from National Health Care Centres. DISCUSSION: The results of this study may contribute to early identification of families at risk for adverse parent-infant relationships, infant development, or parenting. Thereby this study will be relevant for the development of policy, practice, and theory concerning infant mental health.     

Histological validation of ICDAS II and radiological assessment of occlusal carious lesions in permanent teeth

The International Caries Detection and Assessment System (ICDAS) was introduced for a detailed evaluation of dental caries. The aim of the present study was to compare the ICDAS scores and radiologically evaluated caries depths to the histologically evaluated carious lesions in permanent teeth. 84 freshly extracted human teeth were included. Visual examination and scoring of the occlusal aspect were performed according to the ICDAS II criteria after completing a respective e-learning programme to support training in the use of ICDAS. Bucco-lingual digital X-ray images of the teeth were taken. Specimens were then fixed in formalin and embedded in a photocuring one-component methacrylate-based resin. Longitudinal sections were cut and stained with rhodamine B, fuchsin and acetic light green dye to assess the caries extension by light microscopic analysis. Assessing ICDAS II scores and histological findings, a rank correlation coefficient of r = 0.890 could be found. ICDAS II/radiology and histology/radiology showed correlation coefficients of r = 0.658 and 0.661, respectively. Evaluating receiver operating characteristic (ROC) curves, no exact predictability could be found for caries lesions in enamel for both ICDAS II and radiological evaluation. Focussing on deep dentin lesions, values of 0.940 (ICDAS II) and 0.845 (radiology) showed high predictability with respect to the histologically observed caries extension. The present study indicates an acceptable validity of the ICDAS II criteria when applied to permanent teeth. Especially, dentin lesions can be reliably detected. Thus, ICDAS assessment provides the possibility of reducing X-ray exposure for caries detection.