Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers

In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated.     

Fertility and pain outcomes following laparoscopic segmental bowel resection for colorectal endometriosis: a review

Intestinal involvement in endometriosis is thought to occur in up to 12% of all endometriosis cases. While colorectal resection is being increasingly advocated as a feasible management option in patients with severe disease, there still remains significant resistance towards this surgery. This article aims to review the current literature to determine the pain and fertility outcomes following segmental bowel resection for colorectal endometriosis.     

Female sexual function and pelvic floor disorders

OBJECTIVE: To investigate the hypothesis that pelvic floor disorders are associated with female sexual problems, independently of other related factors. METHODS: The study population included 301 adult women seeking outpatient gynecologic and urogynecologic care. Pelvic floor disorders were assessed with the Pelvic Floor Disorders Inventory-20 (PFDI-20) and the pelvic organ prolapse quantification examination. Sexual function was assessed with the Personal Experiences Questionnaire. Using ordinal regression analysis, we identified characteristics and conditions associated with decreased libido, infrequent orgasm, decreased arousal, and dyspareunia. RESULTS: Sexual function was poorer among 78 women (26%) without a current sexual partner than among 223 with a partner (P<.01). Among the 223 with a current partner, women with a high Pelvic Floor Disorders Inventory score were significantly more likely to report decreased arousal (P<.01), infrequent orgasm (P<.01), and increased dyspareunia (P<.01). A similar pattern was observed for the urinary, colorectal-anal, and prolapse scales of the Pelvic Floor Disorders Inventory, although some associations were marginally significant. Stage III-IV prolapse was significantly associated with infrequent orgasm (P=.02), but other sexual complaints were not more common with increasing prolapse stage. CONCLUSION: Pelvic floor symptoms are significantly associated with reduced sexual arousal, infrequent orgasm, and dyspareunia. We conclude that sexual function is worse in women with symptomatic prolapse but not in women with asymptomatic prolapse. LEVEL OF EVIDENCE: II.     

A prospective randomized controlled trial of Wallace and Rocket embryo transfer catheters

The aim of this study was to compare the efficacy of two embryo transfer catheters: Wallace and Rocket Embryon in an IVF programme of a tertiary referral university centre. A total of 308 patients undergoing embryo transfer were prospectively randomized to either a transfer with the Wallace catheter or a transfer with the Rocket catheter. The main outcome measure in this study was the clinical pregnancy rate, and secondary outcome measures included implantation rate, visibility of the catheter under ultrasound, number of retained embryos post transfer, and whether change of catheter was required. In addition, patient discomfort during the procedure was recorded. Pregnancy and implantation rates were similar when Wallace or Rocket catheters were used. However, for the Rocket catheter, the tip was more often clearly seen on ultrasound and it had a lower rate of retained embryos in the catheter after transfer (P < 0.05). Experience with different transfer catheters is recommended for difficult cases.     

Live birth following preimplantation genetic screening for trisomy 21. Should aneuploidy screening be offered to all older patients undergoing IVF?

A 42-year-old female patient with history of secondary infertility was referred to our assisted conception unit for in vitro fertilization (IVF). Before her referral, she had two cycles of IVF at another centre; the first was unsuccessful and, after conceiving at the second attempt, the pregnancy was terminated at 14 weeks' gestation following a positive nuchal translucency scan and a diagnosis of trisomy 21 (Down syndrome) by a chorionic villous biopsy performed in the first trimester. The screening tests for trisomy 21 were offered to the patient in view of her advanced age. Subsequent karyotyping revealed that both partners had a normal chromosomal complement. Following genetic counselling, the couple were offered IVF treatment along with preimplantation genetic screening for trisomy 21. Four of the five embryos were suitable for biopsy, and one blastomere from each embryo was analyzed using fluorescent in situ hybridization for chromosome 21. The analysis revealed that two embryos had trisomy 21, one had monosomy 21, and only one embryo was diploid for chromosome 21. The single diploid embryo was transferred to the uterus on day 3, and resulted in an uneventful pregnancy and delivery of a healthy live-born male.     

STUDIES ON MENINGOCOCCUS INFECTION : X. A FURTHER NOTE ON THE PRESENCE OF MENINGOCOCCUS PRECIPITINOGENS IN THE CEREBROSPINAL FLUID

Precipitin tests have been carried out on spinal fluid from cases of meningococcal and other forms of meningitis, with monovalent anti-meningococcus horse serum of high titer. Using such a test it has been possible within 2 hours to diagnose and type cases of Type I and Type II meningococcal meningitis. In a certain number of cases fluids which were negative when first drawn became positive after standing for 1 or 2 days at 37°C. or room temperature. In 9.5 per cent of all Type I cases the fluids did not become positive. Fluids from cases due to atypical meningococci may react with the type serum of the group to which they belong (i.e., Types II* and VII, which belong to group II, with Type II serum) but do not in every case. Fluids from forms of meningitis other than meningococcal give no reaction. The use of concentrated sera is not advantageous at present, owing to the heterologous reactions which occur.     

STUDIES ON MENINGOCOCCUS INFECTION : V. THE PRESENCE OF MENINGOCOCCUS PRECIPITINOGENS IN THE CEREBROSPINAL FLUID

Precipitin tests, carried out on the cerebrospinal fluid from cases of meningococcal meningitis with monovalent sera, demonstrate the presence in that fluid of type-specific precipitinogens of the meningococcus. Negative results are secured when the spinal fluid is obtained after the commencement of intrathecal serum treatment and also occasionally when the numbers of infecting organisms are very small. The reaction offers an easy and rapid method of ascertaining to which type of meningococcus a particular case of meningitis is due, and facilitates the immediate use of monovalent therapeutic antimeningococcal serum. Typing by means of the precipitin reaction can be confirmed by agglutination of the strain of organism responsible for the infection, if such strain be isolated. Confirmation by means of agglutination has been possible in all the cases discussed in this report. Spinal fluids from other diseases of the meninges and central nervous system fail to give any precipitin reaction with the monovalent sera.