The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

Provision of medical abortion using telemedicine in Brazil

Objective

To evaluate the need for and outcome of self-administered medical abortion with mifepristone and misoprostol in Brazil, provided through Women on Web, a global telemedicine abortion service.

Study Design

A retrospective case review of women from Brazil who contacted Women on Web in 2011. Information from the online consultation, follow-up questionnaire and emails were used to analyze data including demographics, gestational age, outcome of the medical abortion and symptoms that lead to surgical interventions.

Results

The Women on Web website had 109779 unique visitors from Brazil, 2104 women contacted the helpdesk by email. Of the 1401 women who completed the online consultation, 602 women continued their request for a medical abortion. Of the 370 women who used the medicines, 307 women gave follow-up information about the outcome of the medical abortion. Of these, 207 (67.4%) women were 9 weeks or less pregnant, 71 (23.1%) were 10, 11 or 12 weeks pregnant, and 29 (9.5%) women were 13 weeks or more pregnant. There was a significant difference in surgical intervention rates after the medical abortion (19.3% at < 9 weeks, 15.5% at 11–12 weeks and 44.8% at > 13 weeks, p=.06). However, 42.2% of the women who had a surgical intervention had no symptoms of a complication.

Conclusion

There is large need for medical abortion in Brazil. Home use of mifepristone and misoprostol provided through telemedicine is safe and effective. However, after 13 weeks gestation, there is an increased risk of surgical intervention that may be due to the regimen used and local clinical practices in Brazil.

Implications

The current study shows that there is an unmet need for medical abortion in Brazil, a country with legal restrictions on access to safe abortion services. Telemedicine can help fulfill the need and self administration of medical abortion is safe and effective even at late first trimester abortion. Prospective trials are needed to establish safety, effectiveness and acceptability of home use of medical abortion beyond 12 weeks of pregnancy.     

Using telemedicine for termination of pregnancy with mifepristone and misoprostol in settings where there is no access to safe services

Women on Web is a service that uses telemedicine to help women access mifepristone and misoprostol in countries with no safe care for termination of pregnancy (TOP). This study reviews the telemedicine service. After an online consultation, women with an unwanted pregnancy of up to 9 weeks are referred to a doctor. If there are no contraindications, a medical TOP is conducted by mail. After maximising the follow up from 54.8 to 77.6%, 12.6% decided not to do the TOP and 6.8% of the women who did the medical TOP at home needed a vacuum aspiration. Telemedicine can provide an alternative to unsafe TOP. Outcomes of care are in the same range as TOP provided in outpatient settings.     

Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing: lymphoma induction by benzo[a]pyrene, but not by TPA

E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low spontaneous tumour incidence and their increased sensitivity towards the lymphomagen ethylnitrosourea these mice may present an interesting model for short-term carcinogenicity testing. Here, we report on the further exploration of this transgenic mouse model with two additional carcinogens known to have, among others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during the observation period of 40 weeks. B[a]P also induced tumours of the forestomach within this observation period, though at a lower incidence and apparently equally effective in wildtype and transgenic mice. TPA, on the other hand, was unable to induce lymphomas (or tumours in any other organ) in either transgenic or wildtype animals within the observation period of 44 weeks, when applied dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular analysis showed that B[a]P-induced lymphomas in transgenic mice were of T-cell origin, 80% of which had elevated levels of c-myc expression. None of the lymphomas had increased N-myc expression and mutation analysis of the ras-gene family revealed a K-ras mutation in only one out of eight tumours investigated. Also, none of the lymphomas showed aberrant expression of p53 as determined by immunohistochemistry. It is concluded that the E mu-pim-1 mouse model will not be very suitable for short-term carcinogenicity testing in general: only genotoxic chemicals that have the lymphohaematopoietic system as target for carcinogenesis in wild- type mice, appear to be efficiently identified.      

Thoracic empyema: a study of 56 patients

Fifty seven children with thoracic empyema (37 boys and 20 girls) aged less than 12 years were seen at the University of Port Harcourt Teaching Hospital between January 1989 and December 1991. Staphylococcus aureus was the most common organism isolated from the pus of these patients (36 (63%) patients). Pseudomonas aeruginosa, the next most common organism, was isolated in 10 (18%) patients. The most common symptoms at presentation were acute illness with fever and cough (51 (89%) patients). All the patients were treated with closed intercostal tube drainage and appropriate antibiotics. Decortication was resorted to in only one patient. There were two deaths and the overall survival rate was 97%.     

The reversible antithrombin activity of incubated plasma.

The thrombin time of normal citrated plasma is progressively prolonged on incubation in open glass tubes at 37 degrees C. The phenomenon is dependent on the temperature and duration of incubation, on the pH, and on the concentration of calcium ions present. Platelet-rich citrated plasma fails to exhibit augmented antithrombin activity when similarly incubated, and the addition of washed platelets to platelet-poor plasma inhibits this activity. The clot retarding action of incubated plasma against thrombin is also manifested against Arvin (Ancrod), but not against Reptilase-R. This thrombin time lengthening may be inhibited by incubation with anti-antithrombin III antiserum thus indicating that the phenomenon of thrombin time lengthening is consistent with enhanced activity of antithrombin III. It is unlikely that alterations in the activity of alpha2-macroglobulin, is important in the reduced thrombin-coagulability of incubated plasma. Interference with the polymerisation of fibrin monomers by the physico-chemical changes may contribute to the observed phenomenon.     

Hemostatic factors in primary hepatocellular cancer.

Detailed coagulation studies were performed in a group of 19 patients with primary hepatocellular cancer (PHC) and the results were compared statistically with the findings in 19 control subjects. Various funcitonal and immunochemical methods were employed in determining the possible presence of functional or structural coagulant protein abnormalities. The patient group was characterized by prolonged prothrombin times, partial thromboplastin times, and Reptilase times, increased levels of fibrinogen, factor VIII, and factor VIII-related antigen, moderately devreased levels of factor V, factor IX, factor X, antithrombin III, and plasminogen, and reduced levels of factor II and factor VII. Functional, immunochemical, and biochemical analysis failed to detect the presence of acquired protein abnormalities. These findings indicate that hemostatic changes in primary hepatocellular cancer are nonspecific in character. Severe alterations in the plasma levels of one or more of these hemostatic factors may occur.     

Haemostatic factors in Black and White diabetics.

Haemostatic factors in 33 Black and 32 White maturity-onset diabetics were analysed and compared with those in 19 normal Black and 19 White subjects. The Black-White diabetic group comparisons revealed depressed antithrombin (AT) III functional activity, a raised factor VII level and a raised factor V level in females in the White diabetic group. On comparing the White diabetics with their respective controls a rise in factor VIII and fibrinogen activity was demonstrated. These changes are suggestive of a hypercoagulable state in the White maturity-onset diabetic. In contrast, Black diabetics have higher functional AT III levels than their respective controls. This may indicate a protective reaction which would explain in part the reported lower incidence of occlusive vascular disease in this group. Platelet hyperactivity was not demonstrated in the majority of White and Black diabetics. Black diabetics and controls demonstrated higher factor VIII levels than the corresponding White groups, confirming previous observations of raised factor VIII levels among Blacks and suggesting that this feature is a racial characteristic.