Regulation of human interferon production. II. Inhibition of interferon messenger RNA synthesis by 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

Polyinosinic:polycytidylic acid (poly(I:C))-induced synthesis of interferon messenger RNA in a strain of diploid human fibroblasts (FS-4) can be inhibited by 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB).     

Cellular localization of simian immunodeficiency virus in lymphoid tissues. II. In situ hybridization

Lymph nodes and spleens were collected at autopsy and by biopsy from 29 rhesus monkeys infected with simian immunodeficiency virus (SIV). Lymph nodes were classified morphologically into stages of follicular hyperplasia, follicular involution, follicular depletion with normal or expanded paracortices, follicular and paracortical depletion, granulomatous lymphadenitis, or normal. The distribution of SIV RNA was determined by in situ hybridization using a nick translated, 35S labeled, SIVmac DNA probe. Numbers of SIV-infected cells were rare during follicular hyperplasia, numerous during follicular and paracortical expansion, and rare during follicular and paracortical depletion. The splenic morphology reflected that of the lymph nodes; however, the numbers of SIV-positive cells were uniformly lower. SIV RNA was frequently restricted to a single nucleus within multinucleate syncytial cells in two cases of granulomatous lymphadenitis. These results, combined with those of a previous study, provide evidence for antigen trapping in SIV-infected hyperplastic lymph nodes and for widespread viral infection of macrophages and lymphocytes during paracortical expansion.     

Effect of sex of preceding child on birth interval

The study aim was to examine the effect on birth spacing of a prior female child's birth. The study site was a rural health center under observation by staff from the Dayanand Medical College in Ludhiana, India. The sample included 73 pregnant women who were grouped by the sex of the preceding child. The results showed that the average birth interval was significantly shorter for women with a preceding birth of a female child. The average interval in weeks was 90.73 weeks + or - 54.46 weeks for the 41 women who had a prior girl child compared to 133.68 weeks for the male child. When the female child was at a parity of one the birth interval averaged 73.36 weeks, compared to 137.2 weeks for a prior parity of one male child. At parity of two, the average birth interval was 106.2 for a prior girl child and 144.38 for a prior male child. At a parity of three, the average birth interval was 88.22 weeks for a prior girl child and 96.5 weeks for a prior male child. At a parity of four, the average birth interval was 87.66 weeks for a prior girl child and 46.0 weeks for a prior male child. The significant effect of having a prior girl child was evident only at a parity of one. The intervals at a parity of two and three were shorter for girls but not significantly different. The recommendation was that young women and women with low parity be targeted for family planning in order to lengthen the birth interval, regardless of the desire for sons.     

Shocking findings in Manipur

A sero-surveillance program in the state of Manipur, India revealed an alarmingly high rate of HIV infection, detected primarily among intravenous drug users. Previous surveillance had indicated that heterosexual intercourse was the leading mode of HIV transmission, and in 1989, no HIV infections had been detected in Manipur. But in February 1990, 5 HIV-positive cases were reported, and by May 1991, 1263 had been reported -- 93.9% of them among intravenous drug users. This came as shocking news, considering that at the same time only 5131 HIV cases had been reported in all of India. Although Manipur makes up only 0.91% of the country's population, the state's intravenous drug account for 23.1% of the nation's HIV cases. Manipur has an estimated 30,000 drug addicts, approximately 1/2 of which are intravenous drug users. Heroin is easily available in Manipur, due to the fact that the state shares a common international border of 352 km with Myanmar, one of the 3 countries that make up Southeast Asia's heroin producing "Golden Triangle." The author stresses, however, that drug abuse is not the cause of the transmission of HIV. It is the sharing of needles and syringes among intravenous drug users that creates the risk of infection, and preventive measures should reflect that fact. Besides discouraging drug use, preventive measures will require a dual strategy: 1) until they are cured, intravenous drug users should be given sterilized needles and syringes to avoid sharing; and 2) the law needs to be revised so that drug addicts are treated as patients and not as criminals. The Voluntary Health Association of India has begun to discuss such measures with governmental and nongovernmental organizations involved in the prevention and control of AIDS.     

Effect of child loss on contraception acceptance

In India, interviews were conducted with 250 couples who had at least 2 living children and at least 1 son so researchers could examine the effect of child loss on contraceptive usage. The interviewees lived in the area served by the rural health center in Pohir. 67 couples had lost a child. The child loss group had an acceptance rate for contraception of 41.7% compared to 44.8% for the group who had not experienced child loss. The difference was insignificant. Caste, literacy, and parity did not affect contraceptive usage. These findings suggest that child loss does not play a crucial role in contraception acceptance. On the other hand, some studies show that it is a barrier to fertility limitation. Additional studies are needed to resolve the issue of child loss and fertility.     

Phase I and pharmacologic evaluation of intraperitoneal 5-fluoro-2′-deoxyuridine

Summary Intraperitoneal (i.p.) 5-fluoro-2-deoxyuridine (Floxuridine, FUdR, FdUrd) was evaluated in a phase I study at a starting level of 500 mg given on 1 day in 2 I 1.5% dialysate. Escalations within patients were allowed every other cycle. A total of 23 patients (age, 32–78 years) received 108 treatment courses. Local tolerance at all dose levels was excellent, with no cases of drug-related peritonitis being observed. Nausea and vomiting increased in severity in relation to dose and was universal at >3,000 mg ×3 days. One patient each developed grade 1 mucositis as well as diarrhea at a dose of 3,000 mg×3 days and leukopenia and thrombocytopenia at 5,000 mg×3 days. Peritoneal fluid (PF) and plasma (PL) FdUrd profiles were monitored by an HPLC method in 13 subjects, with 7 being studied serially at 2–4 increment doses for up to 6 h. Profiles that exhibited apparent linear pharmacokinetics gave PF drug levels 2–4 logs higher than the PL counterparts, with the latter essentially declining in parallel to the former, indicating that the disposition of FdUrd from the peritoneal compartment is rate-determining. The mean terminal half-life for PF FdUrd was found to be 115 min and mean peritoneal clearance was 25 ml/min. The vast differences in drug levels and AUC found between the PF and the PL profiles suggests a high systemic clearance of FdUrd, which was confirmed in two patients receiving 2 g FdUrd by short i.v. infusion. A disproportionate increase in the plasma FdUrd levels and the corresponding AUC values was found with increasing dose, suggesting a disproportionate increase in the systemic partitioning of FdUrd when doses were escalated within a patient. Substantial levels of peritoneal 5-fluorouracil (FUra) were also detected in most of the subjects. Thus, FdUrd was found to have several desirable properties for i.p. administration: (1) a 2- to 4-log pharmacologic advantage, (2) the absence of local toxicities, and (3) a favorable antitumor spectrum and some evidence of antitumor effects in this phase I and pharmacology study. A 3,000-mg dose given in 2 l 1.5% dialysate for 3 consecutive days exhibited antitumor activity and produced no systemic toxicity except nausea and vomiting, which was controlled by antiemetics. This dose schedule is therefore recommended for phase II trials directed against small-volume disease in the peritoneal cavity, such as may be found in some stages of ovarian and gastrointestinal cancers. In addition, it is suitable for further exploration as a part of regimens including systemic therapy or drugs that modulate the action of fluoropyrimidines.Supported in part by Cancer Center Core Grant CA 14089, by ROI CA 50 412, by an ACS Institutional Grant (IN21Z, to C. R.) and by the Italian-American Foundation award (to N. C.)Deceased     

Compromised kidney graft rejection response in Vervet monkeys after withdrawal of immunosuppressants tacrolimus and sirolimus

BACKGROUND: In nonprimates, organ allografts are often not rejected after withdrawal of immunosuppression. In this study, we examined whether such a phenomenon also occurs in primates. METHODS: Vervet monkeys were transplanted with renal allografts and treated for 60 days with tacrolimus, or tacrolimus plus sirolimus. The drugs were totally withdrawn on day 61. The survival of the monkeys was monitored, and their response to donor- or third party-derived alloantigens was examined in vivo and in vitro. RESULTS: The majority (80-100%) of the grafts survived for at least additional 30 days with no signs of acute rejection. The compromised rejection is donor-specific, because recipient monkeys failed to reject a donor-derived skin graft, but a third-party skin graft was rejected. In vitro mixed lymphocyte reaction and interleukin-2 production in the mixed lymphocyte reaction between the recipients and their donors or between the recipients and a third party had no discernable patterns, and thus did not reflect the in vivo status of the immune system. Although the recipients could not reject the graft acutely after drug withdrawal, the kidney grafts and the donor-derived skin grafts had pathological findings of chronic rejection. CONCLUSIONS: The rejection response of the monkeys to an established graft after withdrawal of immunosuppression is compromised. The compromised rejection is specific and is not due to a permanent alteration of the immune system by the initial drug treatment. The allografts are not inert but have low levels of interaction with the recipient immune system.     

Complement, fetal antigen, and shaking rigors in parturients.

OBJECTIVES: To assess the relationship, if any, between complement, fetal antigen, and shaking rigors during labor and delivery. METHODS: We recruited 13 volunteers for serial blood sampling during labor and childbirth. RESULTS: Complement levels had a small but significant drop (11-15%) immediately following childbirth but had no association with fetal antigen levels or shaking rigors. Fetal antigen levels failed to show any consistent relationship with shaking rigors or the labor and delivery process. CONCLUSION: Shaking rigors do not appear to be associated with changes in either complement or fetal antigen levels. Complement levels remain stable during labor but drop immediately following birth.