A comparison of diagnostic interviews for depression in the Stirling County study: challenges for psychiatric epidemiology

BACKGROUND: High prevalence rates in psychiatric epidemiologic studies raise questions about whether data-gathering procedures identify transient responses rather than clinical disorders. This issue is explored relevant to depression using data from the Stirling County Study. METHODS: The study's customary method, the DPAX (DP for depression and AX for anxiety) was compared with the Diagnostic Interview Schedule (DIS), both of which were administered to a sample of 1396 subjects selected in 1992. Reasons for discordance were analyzed, and demographic correlates of responses to questions about dysphoria were examined. These lay-administered interviews were then compared with clinician-administered interviews that used the Structured Clinical Interview for DSM-III-R (SCID) with 139 subjects. The kappa statistic and logistic regression were used for statistical assessment. RESULTS: For the level of agreement between the DPAX and the DIS for current and lifetime depression, kappa = 0.40 and kappa = 0.33, respectively. Subjects diagnosed only by the DPAX tended to have less education than those diagnosed only by the DIS. Some idioms for dysphoria seemed to work better than others. Using SCID interviews as a clinical standard, the DPAX had 15% sensitivity and 96% specificity and the DIS had 25% sensitivity and 98% specificity. CONCLUSIONS: Comprehension of an interview can be improved by using multiple questions for dysphoria and a simpler mode of inquiry. Clinician-administered interviews tend to corroborate disorders identified in lay-administered interviews but suggest that survey methods underestimate prevalence. Further research is needed to evaluate the validity of both types of interviews, but evidence from a 16-year follow-up evaluation indicates that depression diagnosed by the DPAX is a serious disorder in terms of morbidity and mortality.     

A new model of visceral pain and referred hyperalgesia in the mouse

The generation of transgenic mice that lack or overexpress genes relevant to pain is becoming increasing common. However, only one visceral pain model, the writhing test, is widely used in mice. Here we describe a novel model, chemical stimulation of the colon, which we have developed in mice. Mice of either sex were injected i.v. with 30 mg/kg Evan's Blue for subsequent determination of plasma extravasation. For behavioural testing, they were placed on a raised grid and 50 microl of saline, mustard oil (0.25-2.5%) or capsaicin (0.03-0.3%) was administered by inserting a fine cannula into the colon via the anus. Visceral pain-related behaviours (licking abdomen, stretching, contractions of abdomen etc) were counted for 20 min. Before intracolonic administration, and 20 min after, the frequency of withdrawal responses to the application of von Frey probes to the abdomen was tested. The colon was removed post-mortem and the Evan's Blue content measured. Mustard oil and capsaicin administration evoked dose-dependent visceral pain behaviours, referred hyperalgesia (significant increase in responses to von Frey hairs) and colon plasma extravasation. The peak behavioural responses were evoked by 0.1% capsaicin and by 1% mustard oil respectively. The nociceptive behavioural responses were dose-dependently reversed by morphine (ED50 = 1.9 +/- 1 mg/kg s.c.). We conclude that this model represents a useful tool both for phenotyping mutant mice and for classical pharmacology since information on visceral pain, referred hyperalgesia and colon inflammation can all obtained from the same animal.     

Term delivery following conservative treatment for villoglandular papillary adenocarcinoma of the uterine cervix: report of a case and analysis of the literature

BACKGROUND: Villoglandularpapillary adenocarcinoma (VPA) of the cervix is often indolent, and surgical treatment has a favorable outlook. Risk factors include depth of invasion, lymphovascular invasion, and the presence of other histologic types of cancer. CASE: An amputation of the cervical portio was required to satisfactorily resect a 2.5-cm ectocervical lesion in a 28-year-old nulligravida. A diagnosis of pure VPA with a depth of invasion less than 2 mm was established. During a subsequent pregnancy, second trimester ultrasound showed extreme effacement of her cervix and an abdominal cerclage was placed. The pregnancy continued until delivery of a healthy infant at 36 weeks. CONCLUSIONS: In cases of tumor invasion less than 3 mm, and in the absence of lymphovascular space involvement, extrauterine spread of pure VPA has not been described. When conservative treatment is planned, amputation of the cervical portio may be better suited than conization to the achievement of an adequate margin of resection. Cervical cerclage may be needed to offset the extensive cervical surgery.     

Endocrinological and endometrial factors in recurrent miscarriage

Objective To investigate the endocrinological and endometrial factors in women with unexplained recurrent miscarriage
Design Prospective, case study
Setting Recurrent miscarriage clinic, Jessop Hospital for Women, Sheffield
Participants One hundred and forty-four women with unexplained recurrent (≥ 3) miscarriages
Methods A blood sample was obtained in early follicular phase (day 3–5) to measure follicle stimulating hormone, luteinising hormone, prolactin, androgens and thyroid function; daily blood/urine samples were obtained from mid-follicular phase to measure luteinising hormone until the luteinising hormone surge was identified; endometrial biopsy and a further blood sample for progesterone measurement were obtained in the mid-luteal phase. A transvaginal ultrasonography was performed to evaluate ovarian morphology.
Results Hypersecretion of luteinising hormone or ultrasonographic features of polycystic ovarian disease was present in 8% and 7.8% of women, respectively. The free androgen index was elevated in 14.6% of subjects. In the mid-luteal phase, low progesterone level was found in 17.4% and delayed endometrial development was noted in 27.1% of women. Although women with recurrent miscarriage women and delayed endometrium had significantly lower progesterone levels than those with normal endometrial development, only 8/24 had mid-luteal progesterone levels below 30 nmol/L. Recurrent miscarriage was not associated with hyperprolactinaemia or abnormal thyroid function test.
Conclusions Endocrinological and endometrial abnormalities are present in about a quarter of women with unexplained recurrent miscarriage.     

Global and gene-specific epigenetic patterns in human bladder cancer genomes are relatively stable in vivo and in vitro over time

We used a methylation-sensitive arbitrarily primed PCR technique to analyze, in a nonselective manner, methylation alterations at GC-rich regions of the genome in metachronous tumors and their derived cell lines from two patients with transitional cell carcinoma of the bladder. The methylation status of the majority of evaluable sequences (83%) remained unchanged in the tumors from both patients relative to a panel of normal urothelium samples obtained from individuals free of bladder disease, in which we measured <1% interindividual variation. The 17% of methylation alterations represents sequences altered in either a cancer-specific (3%), tumor-specific (1%), or patient-specific (13%) manner. The proportion of the altered sequences analyzed that were CpG islands corresponds to approximately 7000 CpG islands altered in the genome. Surprisingly, few additional changes in methylation patterns were observed in cell lines derived from the tumors; however, all of the cell lines showed altered methylation in a common set of 3% of evaluable sequences. Three genes known to be aberrantly methylated in bladder cancer (p16, p15, and PAX6) were studied in detail by methylation-sensitive single nucleotide primer extension and showed increased methylation in culture at preexisting methylated sites for all of the exons but no de novo methylation in culture for the promoters in any cell line. Therefore, our investigation provides the first serial as well as parallel quantitation of the global epigenetic stability in two independent bladder cancer genomes over the course of progression and in culture. In addition, our investigation also provides the first direct comparison of the epigenetic and genetic patterns on the global scale, showing the epigenetic pattern to be relatively stable in vivo and in vitro over time within an individual.     

Complete genetic suppression of polyp formation and reduction of CpG-island hypermethylation in Apc(Min/+) Dnmt1-hypomorphic Mice

Promoter CpG island hypermethylation of critical genes is thought to play an important role in human colorectal tumorigenesis. In this study, we show that low levels of CpG island methylation occur in the normal intestinal mucosa of Apc(Min/+) mice and are increased in Multiple Intestinal Metaplasia (Min) polyps. We examined the interaction between CpG island hypermethylation and tumorigenesis by genetically modulating expression levels of the predominant DNA methyltransferase, Dnmt1, in Apc(Min/+) mice. We show that a combination of Dnmt1 hypomorphic alleles results in the complete suppression of polyp formation and an accompanying reduction in the frequency of CpG island methylation in both the normal intestinal mucosa and intestinal adenomas. These results suggest that sufficient DNA methyltransferase expression is a prerequisite for polyp formation and that hypomorphic alleles of Dnmt1 are not merely genetic modifiers but the first identified true genetic suppressors of the Min phenotype.