Contradictory antitumor efficacies produced by the combination of DNA attacking drugs and polyamine antimetabolites

The antitumor effects of two polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), when combined with cis-diamminedichlroplatinum (CDDP) or mitomycin C (MMC), were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO 1000 mg/kg and MGBG 50 mg/kg were given intraperitoneally for 6 successive days, while CDDP 3 mg/kg or MMC 2 mg/kg was given every second day. Although DFMO and MGBG plus MMC did suppress the tumor growth, the combination with CDDP led to no suppression, and rapid growth occurred after the cessation of therapy. The inhibition of tumoral DNA biosynthesis and a decline in polyamine levels, were also not observed. The polyamine antimetabolites when used with CDDP did not produce the desired antitumor efficacy, even though the platinum concentration in the tumor tissue was high. On the contrary, however, DFMO and MGBG when combined with MMC did suppress tumor growth, inhibited DNA biosynthesis, and tissue polyamine levels were low. These results suggest that though CDDP and MMC belong to a similar category of DNA attacking, bifunctional alkylating agents, the findings of these two drugs are contradictory. Here, the mechanism of action no doubt plays a contributory role.     

Clinical results of intraperitoneal hyperthermic perfusion combined with surgery in patients with peritoneal recurrence from gastric cancer

Six patients with peritoneal recurrence after radical operation for gastric cancer were treated by an intraperitoneal hyperthermic perfusion (IPHP) combined with surgery (IPHP group). Immediately after surgery, a 2-hour IPHP was performed, using a perfusate containing 10 micrograms/ml of MMC, warmed at the inflow temperature of 46.5 +/- 1.1 degree C. Within the same period of time, 5 patients with intra-abdominal recurrent gastric cancer (control group) were treated by an intraperitoneal administration of MMC 10 mg combined with surgery. These 11 patients had malignant peritoneal effusion and, although in 3 of the control group, ascitic effusion did re-accumulate rapidly soon after surgery, the 6 patients of IPHP group did not re-accumulate post-hyperthermically. The average survival duration of IPHP group is 13.6 +/- 10. 6 months, whereas that for controls is 3.0 +/- 2.1 months. Again, the survival rate for IPHP group surpassed that for controls at p = 0.012 and p = 0.008, in a generalized Wilcoxon method and Logrank method, respectively. Post-hyperthermically, hypoproteinemia and thrombocytopenia occurred transitorily. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence due to gastric cancer.     

The Moraceae-based dart poisons of South America. Cardiac glycosides of Maquira and Naucleopsis species.

The use of cardenolide-containing Moraceae in the dart poisons of South America is reviewed. Those prepared by the Chocó Indians of western Colombia--called niaará or kieratchi--have probably been made from the latex of Naucleopsis amara and N. glabra. In Ecuador, the Colorado Indians used N. chiguila, while the Coaiquer Indians still derive a poison from the latex of N. naga and the Cayapá Indians occasionally make use of a blowgun poison, hambi, which probably also comes from a Naucleopsis species. The Kaborí (Rio Uneiuxi Makú) Indians of north-western Brazil may have utilized Maquira coriacea, but a more recent collection documents N. mello-barretoi latex as a source of their poison. The Tikuna Indians of western Brazil included leaves and bark of N. stipularis in one of their poisons. The principal cardiac glycosides present in Maquira species are strophanthidin-based and the main ones occurring in Naucleopsis species are antiarigenin- as well as strophanthidin-based. The structures of two new glycosides, isolated from dart-poison samples, have been established as strophanthidin beta-D-glucomethylosido-D-alloside and beta-D-digitoxosido-D-alloside. The former is a major component of pakurin, the crystalline glycoside mixture prepared by Santesson in 1928 from a Chocó Indian poison.     

Presenting characteristics,comorbidities, and outcomes of patients coinfected with COVID-19 and Mycoplasma pneumoniae in the USA

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS-CoV-2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID-19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%-50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, interleukin-6, serum ferritin, and D-dimer in all six (100%) patients. The chest X-ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course.     

Proliferating cell nuclear antigen in malignant and pre-malignant lesions of epithelial origin in the oral cavity and the skin: an immunohistochemical study

Summary Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G₁ and S phase of the cell cycle and immunohistochemical detection of the protein represents a useful marker for the proliferating fraction of cells in tissue specimens. A series of malignant and pre-malignant lesions of the oral cavity and skin were evaluated by the streptavidin biotin immunoperoxidase method for detection of this protein. Monoclonal anti-PCNA antibody (PC 10) labelled proliferating cells in all cases with varying intensity of nuclear staining. In squamous cell carcinoma (n=48), PCNA positivity correlated with the differentiation and atypia of the tumour cells; however, in poorly differentiated tumours, the relationship between PCNA expression and proliferation was lost. Basal cell carcinoma showed an increased growth fraction in tiny epithelial nests (mean 43.8, SD 6.0,n=20) than in neoplastic basal cells (mean 30.1, SD 6.9,n=8). The growth fractions were significantly higher in the pre-malignant lesions (leukoplakia, mean 22.3, SD 7.7,n=14; Bowen's disease, mean 45.2, SD 11.7,n=12; senile keratosis, mean 41.2, SD 7.0,n=12) than in the normal mucosa (mean 9.8, SD 4.9,n=10), suggesting that cellular growth fractions correlate with the degree of dysplasia in pre-malignant lesions.     

Night blindness during pregnancy and subsequent mortality among women in Nepal: effects of vitamin A and beta-carotene supplementation

Night blindness due to vitamin A deficiency is common during pregnancy among women in Nepal. The authors assessed the risk of maternal death during and after a pregnancy with night blindness among women participating in a cluster-randomized, placebo-controlled vitamin A and beta-carotene supplementation trial in Nepal from July 1994 to September 1997. Subjects were 877 women with night blindness and 9,545 women without night blindness during pregnancy. Women were followed from the time they declared that they were pregnant through the end of the study, representing a median follow-up of 90 weeks (interquartile range: 64-121 weeks). Mortality of night-blind women in the placebo group was 3,601 per 100,000 pregnancies. In comparison, the relative risk of dying among nonnight-blind women in the placebo group was 0.26 (95% confidence interval (CI): 0.13, 0.55), and the relative risk among women with or without night blindness in the vitamin A/beta-carotene group was 0.32 (95% CI: 0.10, 0.91) and 0.18 (95% CI: 0.09, 0.36), respectively. Night-blind women were five times (95% CI: 2.20, 10.58) more likely to die from infections than were women who were not night blind. These findings show that night blindness during pregnancy is a risk factor of both short- and long-term mortality among women. Vitamin A/beta-carotene supplementation ameliorates this risk to a large extent.     

Vitamin A or beta-carotene supplementation reduces symptoms of illness in pregnant and lactating Nepali women

The contribution of nutritional interventions to the reduction in maternal morbidity rates in developing countries is not well known. We assessed the impact of weekly vitamin A and beta-carotene supplementation on the prevalence of pregnancy and postpartum illness symptoms among 15,832 Nepali women in a placebo-controlled, double-masked, cluster-randomized trial. There was no impact of either supplement on morbidity rates reported up to 28 wk of gestation, inclusive. However, in late pregnancy (>28 wk), symptoms of nausea, faintness and night blindness were reduced with vitamin A, but not beta-carotene, supplementation. Vitamin A supplementation shortened the length of labor by 1.5 h 50 min among nulliparous and multiparous women, respectively. Both interventions reduced the postpartum prevalence of at least four loose stools and night blindness. beta-Carotene supplementation also reduced symptoms of high fever postpartum. The mean number of days of any reported illness symptoms was 3-4 per wk throughout pregnancy. Among women receiving vitamin A, the total number of days of illness symptoms accrued over the last 12 wk of pregnancy was lower by 5 d compared with the placebo recipients. We found the burden of pregnancy-related illness symptoms to be high in this rural area of Nepal where antenatal care is poor and most deliveries occur at home. Maternal vitamin A or beta-carotene supplementation resulted in a reduction in the prevalence of selected illness symptoms during late pregnancy, at the time of birth and during 6 mo postpartum, suggesting that a diet adequate in vitamin A may be important for improving women's reproductive health.     

Evaluation of a one-stop clinic for the rapid assessment of post-menopausal bleeding.

In this study, we evaluated the management of postmenopausal bleeding at our one-stop clinic where the first line investigations were a transvaginal ultrasound scan and a pipelle endometrial biopsy. The records of 212 women seen in this clinic in 1994 were reviewed. One hundred and forty-four women (67.9%) were evaluated and reassured in one visit. The mean waiting period following referral to the clinic by the general practitioner was 36 days (range 6-157 days), and only 45 women (21%) required a hysteroscopy. The commonest diagnosis made was endometrial atrophy or no significant endometrial pathology (130 women (61.3%). Endometrial cancer was diagnosed in 12 women (5.6%), and one case of previously unsuspected ovarian cancer was detected. Our findings show that most women with post-menopausal bleeding can be assessed in one visit, and hysteroscopy is not always necessary in the initial assessment of this complaint.