At what age should we attempt to retrieve sperm from males with Klinefelter syndrome

Klinefelter syndrome (KS) is a common disorder and almost every clinician in almost every sub-specialty of medicine will knowingly or unwittingly treat boys or men with a 47,XXY chromosomal constitution. Although there are numerous aspects of KS worthy of discussion, this contribution will focus specifically on the controversial, and as yet unresolved, issue of whether it is advantageous to harvest testis tissue from peri-pubertal or adolescent boys with KS in a heroic effort to preserve that child’s chances of reproduction in his future adult life. What would be the rationale for that, how does the biology of spermatogenesis in the Klinefelter testis impact that decision, and what does the data show? The answer, assembled from a selection of seemingly disparate sources and directions, appears to be “No”. We do not have to advocate for an aggressive approach, we do not have to preemptively preserve future fertility. We can justifiably wait until adulthood with equivalent chances of success.     

Bivalent non-typhoidal Salmonella outer membrane vesicles immunized mice sera confer passive protection against gastroenteritis in a suckling mice model

Invasive non-typhoidal Salmonella (iNTS) serovars, especially Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE), cause gastroenteritis worldwide. Due to the emergence of multi-drug resistance in iNTS, a broad-spectrum vaccine is urgently needed for the prevention of iNTS infection. Currently, there is no effective licensed vaccine against iNTS available in the market. We have formulated an outer membrane vesicles (OMVs) based bivalent immunogen as a vaccine candidate to generate broad-spectrum protective immunity against both recently circulating prevalent ST and SE. We have isolated OMVs from ST and SE and formulated the immunogen by mixing both OMVs (1:1 ratio). Three doses of bivalent immunogen significantly induced humoral immune responses against lipopolysaccharides (LPSs) and outer membrane proteins (OMPs) as well as a cell-mediated immune response in adult mice. We also observed that proteins of OMVs act as an adjuvant for generation of high levels of anti-LPS antibodies through T cell activation. We then characterized the one-day old suckling mice model for both ST and SE mediated gastroenteritis and used the model for a passive protection study. In the passive protection study, we found the passive transfer of bivalent OMVs immunized sera significantly reduced ST and SE mediated colonization and gastroenteritis symptoms in the colon of suckling mice compared to non-immunized sera recipients. The overall study demonstrated that OMVs based bivalent vaccine could generate broad-spectrum immunity against prevalent iNTS mediated gastroenteritis. This study also established the suckling mice model as a suitable animal model for vaccine study against iNTS mediated gastroenteritis.     

A study on serum carotenoid levels in breast cancer patients of Indian women in Chennai (Madras), India

Two-hundred and six breast cancer cases were histologically confirmed breast cancer diagnoses at the Cancer Institute in Chennai (Madras), India. One-hundred and fifty hospital controls were patients who had cancer at any site other than breast and gynecological organs, and 61 healthy controls were persons accompanying patients in the Cancer Institute. Serum levels of carotenoids such as beta-carotene, lycopene, cryptoxanthin, and zeaxanthin & lutein were determined by HPLC. Serum levels of total carotenes and total carotenoids including beta-carotene, which reflects food intake of colored vegetables and fruits and has a protective role for certain sites of cancer, were significantly lower among breast cancer cases and hospital controls compared to healthy controls, especially in post-menopausal women. Serum carotenoid levels appeared to change with menopausal status. Serum beta-carotene levels tended to be lower among breast cancer cases than among hospital controls in premenopausal women. Serum xanthophyll levels were significantly lower among breast cancer cases than among healthy controls in post-menopausal women, but not in premenopausal women. Serum levels of retinol and alpha-tocopherol among breast cancer cases were not significantly different from those in post-menopausal healthy controls, but were higher than those in hospital controls. Serum estrone levels were significantly higher among breast cancer cases than among healthy controls, but serum levels of estradiol and estriol were not. In conclusion, Indian women with cancer of breast or of other sites might have low intake of green-yellow vegetables rich in fiber and carotenoids such as beta-carotene and zeaxanthin & lutein.     

Cervical cancer screening in Tamilnadu, India: a feasibility study of training the village health nurse

Uterine cervical cancer is the most common malignancy among females in developing countries, including India. The success of cervical cancer screening programs in North America and Western Europe has been the result of centralized cervical-cytology screening. This is not possible in the villages (n=17,000) of Tamilnadu where 58 percent of females in rural areas are illiterate, health infrastructure is mediocre, and cervical cytology is unknow. The present study was undertaken to examine if the village health nurse (VHN) could be trained quickly to identify a cervical abnormality by visual inspection so that we could down stage the cancer to earlier stages, more amenable to treatment. VHNs also would be trained to take an adequate Pap smear. A total of 101 VHNs were trained in batches and returned to their villages. Within two years, 6,459 engible women in the study area were screened. The agreement between the gynecologists and the VHNs in identifying cancer among those with abnormal cervix was 95 percent, and 80 percent of the Pap smears taken by VHNs were adequate by WHO criteria, making the feasibility study highly successful.Authors are with The Cancer Institute (WIA), Adyar, Madras, Tamil Nadu,India. Address correspondence to Dr Gajalakshmi, Epidemiology Division and Cancer Registry, 18, Sardar Patel Road, Cancer Institute (WIA), Madras-600 036, Tamilnadu, India. This project was funded by the Indian Council of Medical Research, Government of India, New Delhi, India.520 Cancer Causes and Control. Vol 7. 1996     

Registration of cancer mortality data in a developing area: Chennai (Madras, India) experience

Objectives: This study was carried out to evolve a method to improve the registration of cancer mortality data in Chennai (Madras, India). Methods: Data on cancer deaths have been collected from the Vital Statistics Department (VSD) by a population-based cancer registry (PBCR) in Chennai only since 1982. The low mortality-to-incidence ratio during 1982-84 suggested under-registration of mortality data. Since 1985, the PBCR has taken special effort to ascertain the vital status of cancer cases by sending reply-paid postcards and/or making house visits. The data on all deaths occurring in Chennai, irrespective of stated cause of death in the death certificate, have been collected from the VSD since 1992. Results: Deaths that occurred in Chennai and obtained by sending reply-paid postcards and/or making house visits were registered in VSD as non-cancer causes of death; hence, these data were not collected from VSD. The sensitivity and positive predictive values of death certificates on cancer diagnosis based on 1992 and 1993 mortality data were 57 percent and 99.5 percent, respectively. Conclusion: Since the accuracy of death certificate information on cancer diagnosis is relatively low in a developing country such as in India, collecting data on all deaths will improve the mortality data registration in PBCRs.     

Horizontal transmission of novel H1N1/09 influenza virus in a newborn: Myth or fact?

Horizontal transmission of H1N1/09 virus infection is very common however; transmission through this route has not been reported in newborns. To our knowledge, this is the first case report of newborn who acquired infection of novel H1N1/09 virus horizontally through asymptomatic family members or hospital staff during epidemic period in Kolkata, India. Baby recovered without antiviral therapy but received antibiotic for bacterial co-infection.     

Cover Image,Volume 20, Issue 4

The cover image, by Inmaculada Ruz‐Maldonado et al., is based on the Original Article LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling, DOI: 10.1111/dom.13180 .

     

Rapamycin has suppressive and stimulatory effects on human plasmacytoid dendritic cell functions

Plasmacytoid dendritic cells (PDC) are involved in innate immunity by interferon (IFN)-α production, and in adaptive immunity by stimulating T cells and inducing generation of regulatory T cells (T_reg). In this study we studied the effects of mammalian target of rapamycin (mTOR) inhibition by rapamycin, a commonly used immunosuppressive and anti-cancer drug, on innate and adaptive immune functions of human PDC. A clinically relevant concentration of rapamycin inhibited Toll-like receptor (TLR)-7-induced IFN-α secretion potently (−64%) but TLR-9-induced IFN-α secretion only slightly (−20%), while the same concentration suppressed proinflammatory cytokine production by TLR-7-activated and TLR-9-activated PDC with similar efficacy. Rapamycin inhibited the ability of both TLR-7-activated and TLR-9-activated PDC to stimulate production of IFN-γ and interleukin (IL)-10 by allogeneic T cells. Surprisingly, mTOR-inhibition enhanced the capacity of TLR-7-activated PDC to stimulate naive and memory T helper cell proliferation, which was caused by rapamycin-induced up-regulation of CD80 expression on PDC. Finally, rapamycin treatment of TLR-7-activated PDC enhanced their capacity to induce CD4⁺forkhead box protein 3 (FoxP3)⁺ regulatory T cells, but did not affect the generation of suppressive CD8⁺CD38⁺lymphocyte activation gene (LAG)-3⁺ T_reg. In general, rapamycin inhibits innate and adaptive immune functions of TLR-stimulated human PDC, but enhances the ability of TLR-7-stimulated PDC to stimulate CD4⁺ T cell proliferation and induce CD4⁺FoxP3⁺ regulatory T cell generation.