We report here results of clinical trials on a birth control vaccine, consisting of a heterospecies dimer of the .3 subunit of human chorionic gonadotropin (hCG) associated noncovalently with the a subunit of ovine luteinizing hormone and coijugated to tetanus and diphtheria toxoids as carriers, that induces antibodies of high avidity (Ka 1010 M-) against hCG. Fertile women exposed to conception over 1224 cycles recorded only one pregnancy at antibody titers of >50 ng/ml (hCG bioneutralization capacity). The antibody response declines with time; fertility was regained when titers fell to <35 ng/ml. This study presents evidence of the feasibility of a vaccine for control of human fertility.A number of contraceptive methods are available; they do not, however, suit all potential users. There is need to develop additional methods, in particular those that are reversible, require only periodic intake, and do not disturb menstrual regularity or bleeding. Vaccines regulating fertility offer promising prospects to meet these specifications. The rationale for these vaccines is to induce the formation of antibodies and/or cell-mediated immunity to intercept selectively a process critical to the success of reproduction. A number of potential antigens are being investigated (1-7). Among these are hormones, which play an important role in the regulation of fertility. Human chorionic gonadotropin (hCG) is an early signal of conception and is considered essential for establishment and maintenance of early pregnancy. An advantage in choosing hCG as a target for immunocontraception is that its inactivation would not interfere with other physiological processes in the female, such as ovulation and production of sex steroid hormones.Carrier conjugation with tetanus toxoid (TT) was proposed as a strategy to overcome the immunological tolerance of a woman against hCG (8). This initial prototype vaccine (/3hCG-TT adsorbed on alum) had limitations. It induced high antibody titers in only a small percentage of women, and those with low titers were not protected from pregnancy (9). Three changes were made to enhance immunogenicity.(i) An adjuvant, the sodium phthalyl derivative of lipopolysaccharide, was included in the first injection. This nonpyrogenic adjuvant is usable in aqueous phase (10). Its use doubled, on average, anti-hCG titers and increased the frequency of high responders.(ii) The intrinsic immunogenicity of (3hCG was enhanced by associating it noncovalently with the a subunit of ovine luteinizing hormone (LH) to form a heterospecies dimer (HSD), a laboratory-made hormone that attains a conformation which recognizes receptors on target tissues (whereas isolated subunits do not) and generates a steroidogenic response even superior to that by hCG (11). HSD linked to carriers was indeed found to be more immunogenic than ,8hCG in rats and monkeys (12). Moreover, the antibodies had better capacity to neutralize the bioactivity of hCG (11,13 It was important to determine whether the antibodies induced by the HSD-and 8hC...

No abstract

PURPOSE Globally, colorectal cancer (CRC) ranks third in terms of incidence and second in terms of mortality. A relatively low burden of CRC has been reported from low- and middle-income countries (LMIC), and there is a paucity of publications related to CRC from LMIC. PATIENTS AND METHODS A computerized comprehensive structured CRC clinical database was developed. All the patients with histopathologically proven CRC undergoing either curative and palliative multimodality management or surgical interventions between 2000 and 2019 were included in the study. A descriptive analysis of the demographic profile and clinical spectrum was performed. RESULTS A total of 970 patients of CRC were treated between 2000 and 2019. Of these, 401 patients (41.3%) had colon cancer and 569 (58.7%) had rectal cancer. The male-to-female ratio was 1.79:1. The mean age at presentation was 47.7 years. A total of 337 (34.7%) patients qualified as young CRC (≤ 40 years of age at diagnosis). The commonest symptom among patients with colon cancer was abdominal pain; 55.6% of patients had a right-sided primary tumor as compared with 42.2% with left-sided tumors. The commonest symptom among patients with rectal cancer was bleeding per rectum. The predominant location of the tumor was in the lower rectum (58%). Majority of patients with CRC presented with locally advanced stage II and III disease. The most common histologic subtype encountered for both colon and rectal cancers was adenocarcinoma (84.8% and 81.2%, respectively). CONCLUSION This study has revealed certain important findings related to CRC in LMIC including a higher burden of young colorectal cancer, a relatively higher proportion of rectal cancers in comparison with colon cancer, a high percentage of patients with low-rectal cancer, and advanced stage at presentation.

No abstract