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Biomedical subjects

L Mascarenhas

Publications and source records attributed to L Mascarenhas.

At least 19 recordsLinked to original sources

Successful outcome of advanced abdominal pregnancy with exclusive omental insertion.

We report the case of an advanced abdominal pregnancy with exclusive omental insertion whose extrauterine location was not established until delivery by Cesarean section at 35 weeks' gestation. It is hard to believe that omental placentation alone would be sufficient to sustain a pregnancy beyond a gestation where the fetus is viable. However, this report challenges such myths and opens the debate as to what represents the minimal placental maternal viscus contact necessary to achieve fetal viability. The case also demonstrates the continuing difficulty in diagnosing this rare but serious condition despite advances in obstetric imaging, and advocates methods to avoid missing the diagnosis, which could be easily incorporated at booking and mid-trimester scans. Apart from this case, few reports describe normal umbilical artery Doppler velocimetry in advanced abdominal pregnancy. There is a paucity of research on suitable clinical investigations prognostic for abdominal pregnancy, although this case provides further evidence for the use of Doppler as a useful surveillance tool in such cases. Finally, this case propagates the ethical and clinical controversy that exists in managing abdominal pregnancy, particularly when diagnosed late after attaining fetal viability. Expectant management may represent a feasible alternative to surgical termination provided the woman is fully informed of the attendant risks and close surveillance of the pregnancy is undertaken.

Adult↗

Endometrial effects of etonogestrel (Implanon) contraceptive implant.

The subdermal contraceptive implant etonogestrel (Implanon; NV Organon International, Oss, The Netherlands) exerts complex effects on the endometrium. These include direct effects on the endometrium through endometrial progestin target sites, and indirect effects through suppression of the hypothalamic-pituitary-ovarian axis. The resulting effects are categorized by alterations in endometrial histology, endometrial thickness, dysmenorrhoea and menstrual bleeding pattern. The exact mechanism of action of progestins on the endometrium has not been determined. The contraceptive effect in Implanon users is mainly due to inhibition of ovulation. Current research is concentrating on the potential of the progestin implant to modify endometrial vascular, angiogenic, steroid receptor and proto-oncogene function. These processes may be involved in the causation of progestin-induced breakthrough bleeding.

Contraceptive Agents, Female↗

Lentiviral vectors for efficient delivery of CD80 and granulocyte-macrophage- colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid leukemia cells to induce antileukemic immune responses.

Cell vaccines engineered to express immunomodulators have shown feasibility in eliminating leukemia in murine models. Vectors for efficient gene delivery to primary human leukemia cells are required to translate this approach to clinical trials. In this study, second-generation lentiviral vectors derived from human immunodeficiency virus 1 were evaluated, with the cytomegalovirus (CMV) promoter driving expression of granulocyte-macrophage-colony-stimulating factor (GM-CSF) and CD80 in separate vectors or in a bicistronic vector. The vectors were pseudotyped with vesicular stomatitis virus G glycoprotein and concentrated to high titers (10(8)-10(9) infective particles/mL). Human acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia cell lines transduced with the monocistronic pHR-CD80 vector or the bicistronic pHR-GM/CD vector became 75% to 95% CD80 positive (CD80(+)). More important, transduction of primary human ALL and AML blasts with high-titer lentiviral vectors was consistently successful (40%-95% CD80(+)). The average amount of GM-CSF secretion by the leukemia cell lines transduced with the pHR-GM-CSF monocistronic vector was 2182.9 pg/10(6) cells per 24 hours. Secretion was markedly lower with the bicistronic pHR-GM/CD vector (average, 225.7 pg/10(6) cells per 24 hours). Lower amounts of CMV-driven messenger RNA were detected with the bicistronic vector, which may account for its poor expression of GM-CSF. Primary ALL cells transduced to express CD80 stimulated T-cell proliferation in an autologous mixed lymphocyte reaction. This stimulation was specifically blocked with monoclonal antibodies reactive against CD80 or by recombinant cytotoxic T-lymphocyte antigen 4-immunoglobulin fusion protein. These results show the feasibility of efficiently transducing primary leukemia cells with lentiviral vectors to express immunomodulators to elicit antileukemic immune responses. (Blood. 2000;96:1317-1326)

Acute Disease↗

Insertion and removal of Implanon: practical considerations.

Implanon, a novel contraceptive implant containing the progestogen, etonogestrel (68 mg), provides highly effective, well-tolerated contraception for up to 3 years. Its single-rod design, semi-rigid polymer base and convenient pre-loaded presentation mean that Implanon has potential insertion and removal advantages over the six-capsule Norplant implant. Insertion of Implanon is simple: the applicator needle is positioned subdermally and the cannula is withdrawn, leaving the implant rod in place. Implanon is removed using the 'pop out' technique, involving a 2-mm incision. A meta-analysis of data from seven open-label, randomized studies in 1,378 women compared the ease of insertion and removal of the Implanon and Norplant implants and the frequency of associated complications. It was approximately four times quicker to insert and remove Implanon than Norplant (mean insertion times 1.1 vs. 4.3 min, respectively; mean removal times 2.6 vs.10.2 min, respectively). Insertion complications were very rare with both Implanon (0.3%) and Norplant (0.0%). However, Implanon was associated with a significantly lower frequency of removal complications (0.2 vs. 4.8% with Norplant; p < 0.001). Implant site abnormalities were uncommon. The simplicity of the insertion and removal procedures with Implanon may have significant implications for contraceptive implant training programs and user counselling.

Contraceptive Agents, Female↗

Gene delivery to human B-precursor acute lymphoblastic leukemia cells.

Autologous leukemia cells engineered to express immune-stimulating molecules may be used to elicit antileukemia immune responses. Gene delivery to human B-precursor acute lymphoblastic leukemia (ALL) cells was investigated using the enhanced green fluorescent protein (EGFP) as a reporter gene, measured by flow cytometry. Transfection of the Nalm-6 and Reh B-precursor ALL leukemia cell lines with an expression plasmid was investigated using lipofection, electroporation, and a polycationic compound. Only the liposomal compound Cellfectin showed significant gene transfer (3.9% to 12% for Nalm-6 cells and 3.1% to 5% for Reh cells). Transduction with gibbon-ape leukemia virus pseudotyped Moloney murine leukemia virus (MoMuLV)-based retrovirus vectors was investigated in various settings. Cocultivation of ALL cell lines with packaging cell lines showed the highest transduction efficiency for retroviral gene transfer (40.1% to 87.5% for Nalm-6 cells and 0.3% to 9% for Reh cells), followed by transduction with viral supernatant on the recombinant fibronectin fragment CH-296 (13% to 35.5% for Nalm-6 cells and 0.4% to 6% Reh cells), transduction on human bone marrow stroma monolayers (3.2% to 13.3% for Nalm-6 cells and 0% to 0.2% Reh cells), and in suspension with protamine sulfate (0.7% to 3.1% for Nalm-6 cells and 0% for Reh cells). Transduction of both Nalm-6 and Reh cells with human immunodeficiency virus-type 1 (HIV-1)-based lentiviral vectors pseudotyped with the vesicular stomatitis virus-G envelope produced the best gene transfer efficiency, transducing greater than 90% of both cell lines. Gene delivery into primary human B-precursor ALL cells from patients was then investigated using MoMuLV-based retrovirus vectors and HIV-1-based lentivirus vectors. Both vectors transduced the primary B-precursor ALL cells with high efficiencies. These studies may be applied for investigating gene delivery into primary human B-precursor ALL cells to be used for immunotherapy.

Cation Exchange Resins↗

Twenty-four month comparison of apolipoproteins A-1, A-II and B in contraceptive implant users (Norplant and Implanon) in Birmingham, United Kingdom.

A 2-year prospective, randomized study of 60 implant users was performed to evaluate fasting serial serum apolipoprotein A-I, A-II, and B levels before insertion and every 3 months in users of two contraceptive implants releasing levonorgestrel (Norplant) and 3-ketodesogestrel/etonogestrel (Implanon) in Birmingham, United Kingdom. All changes in serum apolipoprotein concentrations, irrespective of an increase or decrease, were smaller than one standard deviation of the mean concentration at baseline and did not exceed the normal range for the laboratory, thus implying no evidence of an increased risk of coronary heart disease.

Adolescent↗

RETRACTED: Insertion and removal of Implanon.

Implanon is a single-rod contraceptive implant containing the progestin etonogestrel. Implants require insertion and removal by medical professionals. Detailed and unbiased counseling before insertion is essential, and should include contraceptive efficacy, insertion and removal procedures, and possible adverse events. Insertion and removal times have been measured in six open studies and in seven comparative studies in which Norplant (the six-capsule levonorgestrel implant) was used as the reference product. In comparative studies, the mean time needed for insertion of Implanon was 1.1 min and removal took 2.6 min. Insertion as well as removal of Implanon was four times faster than with Norplant. Complications with insertion and removal are rare in the hands of medical professionals familiar with the techniques.

Adolescent↗

A 2-year comparative study of endometrial histology and cervical cytology of contraceptive implant users in Birmingham, UK.

The objectives of this study were to evaluate the endometrial histology and cervical cytology of users of two contraceptive implants releasing etonogestrel/3-keto-desogestrel (Implanon) and levonorgestrel (Norplant) in West Midlands (UK) users. A 2-year prospective randomized design was used to study 60 implant users. Endometrial histology and cervical cytology were compared before insertion and after 12 and 24 months. At the end of 12 months, the majority of samples were inactive/weakly proliferative in both groups. At the end of 24 months, this remained unchanged in the Implanon group whereas the pattern was more diverse in the Norplant group. Endometrial thickness was significantly reduced in both groups during treatment. Cervical cytology remained unchanged. It is concluded that, after 2 years, there was no evidence of an increasing risk of endometrial hyperplasia, endometrial carcinoma, cervical intra-epithelial neoplasia or cervical carcinoma in either of the two groups of implant users.

Adolescent↗

Persistent ectopic pregnancy following conservative surgery for tubal pregnancy.

OBJECTIVE: To audit the incidence and management of persistent ectopic pregnancy following conservative tubal surgery performed at laparotomy and via the laparoscope. DESIGN: A retrospective analysis of the case records. SETTING: The Birmingham and Midland Hospital for Women. PARTICIPANTS: Two hundred and fourteen women who received surgical treatment for ectopic pregnancy between October 1991 and December 1994. RESULTS: Of the 85 women who underwent conservative tubal surgery, nine were diagnosed as having persistent ectopic pregnancy on the basis of hCG values. The incidence after laparoscopy was no higher than after laparotomy. A second surgical procedure was indicated in only four cases. CONCLUSIONS: Post-operative surveillance of serum hCG remains mandatory. Patients who remain symptom free may be managed conservatively The threshold for a second-look laparoscopy should be relatively high and be based on the presence of symptoms rather than changes in hCG values.

Chorionic Gonadotropin↗

Controlled ovarian hyperstimulation: an adjunct to assisted reproductive technology.

Controlled ovarian hyperstimulation was given to a study group consisting of male factor, endometriosis, and unexplained infertility. The aim of the study was to determine whether COH might be of value for such couples in a setting lacking ART facilities. When compared with their own spontaneous cycles or with a control group (untreated but scanned), COH proved significantly better for unexplained infertility. However, COH was not significantly effective for male factor infertility. This study shows that COH should be offered routinely in general hospitals to couples on long-term waiting lists for ART (especially those facing enforced expectant management).

Adult↗