Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors.

OBJECTIVE: Although endometriosis and uterine leiomyomas are common conditions, the extent to which either is associated with certain types of malignancies remains uncertain. METHODS: Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for endometriosis or leiomyomas and the development of ovarian and uterine cancers in Denmark between 1978 and 1998. Based on a population-based cohort exceeding 99,000 women, including 2,491 ovarian cancers, 860 borderline ovarian tumors, and 1,398 uterine cancers, we derived relative risks (RR) and 95% confidence intervals (95% CI) associated with overall and histology-specific tumor risks after adjustment for calendar time and reproductive characteristics. RESULTS: Endometriosis seemed to predispose to the development of ovarian cancer, with the association restricted to endometrioid or clear cell malignancies. Five or more years after the diagnosis of endometriosis, the RRs (95% CIs) were 2.53 (1.19-5.38) for endometrioid (7 exposed cases) and 3.37 (1.24-9.14) for clear cell (4 exposed cases) malignancies. Uterine leiomyomas were associated with increases in the risk of uterine malignancies, particularly sarcomas, where the RRs (95% CIs) were 20.80 (11.32-38.22) for women with 1 to 4 years of follow-up (11 exposed cases) and 5.70 (2.27-14.32) for those with more extended follow-up (5 exposed cases). CONCLUSION: In combination with clinical, pathologic, and molecular data, our results support that some endometriotic lesions may predispose to clear cell and endometrioid ovarian cancers. Uterine leiomyomas also showed a strong connection with subsequent uterine sarcomas, although it was difficult to decipher whether this reflected detection bias, shared risk factors, or an etiologic relationship.     

Case-control study of risk factors for cervical neoplasia in Denmark. I: Role of the "male factor" in women with one lifetime sexual partner

Possible risk factors for cervical cancer were investigated in 645 women, 20-49 years of age from Copenhagen, with histologically confirmed cervical cancer or carcinoma in situ and in 614 controls drawn at random from the female population of the same area. To study the role of the "male factor", monogamous cases and controls together with their husbands were invited for further examination. This included a personal interview, a blood sample for analysis of herpes simplex virus antibodies, and a penile swab for papillomavirus analysis. In total, 41 case couples and 90 control couples were enrolled (89% and 92% of eligibles, respectively). The most significant risk determinants were a history of genital warts in the male (RR = 17.9 for ever vs. never) and ever having used condoms (RR = 0.2). Other potentially important factors, although not statistically significant, were ever having visited prostitutes (RR = 2.6, p = 0.14), circumcision (RR = 0.3, p = 0.18), and a history of genital warts in the female (RR = 4.6), p = 0.09). Having a husband with a history of multiple sexual partners was also associated with an increased crude risk, but when adjustment was made for husband ever having had genital warts, use of condom, and age, no significant excess risk was observed. Human papillomavirus DNA, which was tested for with ViraPap and ViraType, was detected in one of the controls, and in only 2 case husbands. This study points to the importance of "high-risk males" for the development of cervical cancer in their sexual partner; the results support the infectious nature of the disease.     

Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients

Background

Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy.

Materials and methods

Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015. End points were number of completed Ra-223 cycles, overall survival (OS) and radiographic progression-free survival (rPFS). Bone scintigraphy, CT of thorax and abdomen, hematological status, PSA and alkaline phosphatase were evaluated prior to first dose and after 3rd and 6th treatment, respectively. Follow-up period was 18 months after first Ra-223 cycle.

Results

A total of 50 consecutive patients initiated Ra-223 therapy in the time period. Seventeen of 50 patients (34%) had prolonged interval between cycles due to delivery problems. Median delay was 4 weeks (range 3–9 weeks). Patients with delayed treatment had significantly longer median rPFS [delayed patients: 7.1 months (95% CI 4.9–9.3) vs. 4.5 months (95% CI 2.8–6.3)]. There was no significant difference in number of completed cycles or median OS.

Conclusion

We find no negative impact of prolonged interval between Ra-223 cycles due to non-disease related reasons on OS, rPFS or number of completed treatment cycles.

     

Effect of arm-cranking on leg blood flow and noradrenaline spillover during leg exercise in man.

Controversy exists whether recruitment of a large muscle mass in dynamic exercise may outstrip the pumping capacity of the heart and require neurogenic vasoconstriction in exercising muscle to prevent a fall in arterial blood pressure. To elucidate this question, seven healthy young men cycled for 70 minutes at a work load of 55-60% VO2max. At 30 to 50 minutes, arm cranking was added and total work load increased to (mean +/- SE) 82 +/- 4% of VO2max. During leg exercise, leg blood flow average 6.15 +/- .511 minutes-1, mean arterial blood pressure 137 +/- 4 mmHg and leg conductance 42.3 +/- 2.2 ml minutes-1 mmHg-1. When arm cranking was added to leg cycling, leg blood flow did not change significantly, mean arterial blood pressure increased transiently to 147 +/- 5 mmHg and leg vascular conductance decreased transiently to 33.5 +/- 3.1 ml minutes-1 mmHg-1. Furthermore, arm cranking doubled leg noradrenaline spillover. When arm cranking was discontinued and leg cycling continued, leg blood flow was unchanged but mean arterial blood pressure decreased to values significantly below those measured in the first leg exercise period. Furthermore, leg vascular conductance increased transiently, and noradrenaline spillover decreased towards values measured during the first leg exercise period. It is concluded that addition of arm cranking to leg cycling increases leg noradrenaline spillover and decreases leg vascular conductance but leg blood flow remains unchanged because of a simultaneous increase in mean arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ectrodactyly and Germany's eugenics law of 14 July 1933

The family reported herein serves as a genetically and historically important vignette on the issues of nonpenetrance (versus germinal mosaicism) in nonsyndromic autosomal dominant ectrodactyly and the Eugenics Law of Germany of 14 July 1933, which was used to coerce the sterilization of the propositus despite infertility in his first marriage. In a sibship of seven children (with normal parents), three boys were affected. The propositus (adoptive grandfather of the author) was the patient of Paul Leopold Friedrich and Georg Perthes, who published their observations on the propositus. Except for an adopted daughter, the propositus was childless. His two affected brothers each had an affected child, and the father- to son transmission confirmed the hypothesis of autosomal dominant inheritance. The issue of nonpenetrance versus germinal mosaicism in ectrodactyly was debated by Auerbach [1956:Ann Hum Genet 20:266-269] and Vogel [1958:Ann Hum Genet 22:132-137], and remains unresolved.     

The effect of intravenous dexamethasone on postoperative nausea and vomiting after Cesarean delivery with intrathecal morphine: a randomized-controlled trial

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - Intrathecal morphine administered during spinal anesthesia for Cesarean delivery is associated with a high incidence of...     

Suggestive linkage to a neighboring region of IRF6 in a cleft lip and palate multiplex family

Cleft lip and/or palate (CL/P) is a common congenital malformation with a complex etiology, as many genes and environmental factors have been shown to play a role in craniofacial development. We used a genetic mapping approach to analyze a family with multiplex CL/P. A genome-wide scan with a 10 kb single nucleotide polymorphism (SNP) chip followed by fine mapping with microsatellite markers in a CL/P multiplex family suggested linkage (maximum multipoint LOD score of 2.41) to a 6.5 Mb interval at 1q32.1-q32.2. This interval was close to, but excluded IRF6. Mutations in the IRF6 (1q32.2) cause syndromic forms of CL/P, and several association studies have shown that polymorphisms in and around IRF6 are associated with non-syndromic CL/P (NSCLP). However, in the family described here, IRF6 was excluded from the linkage interval. Sequencing of selected genes in the interval and comparative genome hybridization (CGH) did not reveal any mutations or genomic aberrations. Our data suggest that an unidentified CL/P gene, or a non-coding IRF6 regulatory element in this linkage interval may have caused CL/P in this family.     

Branchio-oto-renal syndrome: detection of EYA1 and SIX1 mutations in five out of six Danish families by combining linkage, MLPA and sequencing analyses

The branchio-oto-renal (BOR) syndrome is an autosomal-dominant disorder characterized by hearing loss, branchial and renal anomalies. BOR is genetically heterogeneous and caused by mutations in EYA1 (8q13.3), SIX1 (14q23.1), SIX5 (19q13.3) and in an unidentified gene on 1q31. We examined six Danish families with BOR syndrome by assessing linkage to BOR loci, by performing EYA1 multiplex ligation-dependent probe amplification (MLPA) analysis for deletions and duplications and by sequencing of EYA1, SIX1 and SIX5. We identified four EYA1 mutations (c.920delG, IVS10-1G>A, IVS12+4A>G and p.Y591X) and one SIX1 mutation (p.W122R), providing a molecular diagnosis in five out of the six families (83%). The present, yet preliminary, observation that renal and temporal bone malformations are less frequent in SIX1-related disease suggests a slightly different clinical profile compared to EYA1-related disease. Unidentified mutations impairing mRNA expression or further genetic heterogeneity may explain the lack of mutation finding in one family despite LOD score indications of EYA1 involvement.