Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.     

Interactions of herbicides 2,4-D and dinoseb with liver mitochondrial bioenergetics

The use of drugs for common pregnancy complications like premature labor, hypertensive diseases, and premature rupture of membranes with chorioamnionitis is reviewed. In addition, new publications on antiviral drugs in HIV-positive pregnant patients are also discussed. Among the drugs, suppressing premature labor side-effects of beta-mimetics are of growing concern. The effectiveness of other agents like magnesium, indomethacin, and sulindac are addressed. The various mechanisms explaining the beneficial effect of magnesium in pre-eclampsia are reviewed and new data on antihypertensives, such as labetalol, calcium channel blockers, and methyldopa are presented. The evidence from various clinical trials on the value of low-dose aspirin as a prophylactic agent against pregnancy-induced hypertension, pre-eclampsia, and intrauterine growth retardation in high-risk and low-risk patients is compared. Pharmacokinetic data including transplacental transfer of antibiotics and anti-HIV nucleosides are part of this review.     

Imaging of follicular dendritic cell tumours of the liver

Follicular dendritic cell tumour of the liver is a recently recognized entity. To date, only two cases have been described, both in the pathology literature. Histologically, it resembles an inflammatory pseudotumour and immunohistochemical and ultrastructural studies are required for its diagnosis. The ultrasound, computed tomography and angiographic features of two cases of follicular dendritic cell tumour of the liver are described in detail. One of the patients had multiple recurrences of this tumour. The imaging features are very similar to those of hepatocellular carcinoma. As follicular dendritic cell tumour is considered to be of low-grade malignant potential, in contrast to the dismal prognosis for hepatocellular carcinoma, it is important to be able to accurately distinguish between the two types of tumour prior to initiating definitive therapy.     

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.     

Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.     

Ambulatory management of multiple gestation

Ambulatory management of multiple gestation requires careful and continuing care by the obstetrician. The initial evaluation should include a comprehensive history, including use of fertility enhancing drugs and ART, family history, social history; a general physical examination, including a pelvic examination; laboratory evaluation, including complete blood cell count, dipstick urinalysis for protein and glucose, urine culture, blood type, Rh factor and irregular blood antibody determination, serology for rubella, syphilis, hepatitis B surface antigen and varicella (if there is no history). A Papanicolaou smear should be done at the time of the pelvic examination, as should evaluation for bacterial vaginosis. Ultrasound assessment of placentation should be done at 14 weeks' gestation, but vaginal or perineal ultrasound of cervical length should be done at the initial visit. Other testing procedures should include repeat ultrasound evaluation for fetal growth every 4 weeks in a dichorionic placentation and every 3 weeks if monochorionic placentation is present. Triple screen MSAFP at 16-18 weeks' gestation and blood sugar screening at 22-26 weeks should be performed. After the first trimester, the patient should schedule physician visits every 2 weeks or less. Routine medications should include one prenatal vitamin per day, additional folic acid supplementation of 1.0 mg per fetus, supplemental iron preparation, and additional calcium to equal 1500 mg/day. The use of low-dose aspirin to prevent preeclampsia in twin gestations has not been adequately studied. Continuing vigilance by the knowledgeable obstetrician should occur. Multiple gestations should not be cared for by non-physician providers or by family physicians. Referral to a maternal-fetal medicine unit is recommended.     

Ultrastructural and immunocytochemical features of a case of neuroendocrine carcinoma developing in a prior ileostomy site

A patient who developed a mixed neuroendocrine carcinoma and adenocarcinoma at the site of a previous long-standing ileostomy is reported. The neuroendocrine features are documented by both ultrastructural and immunocytochemical findings. Carcinoma arising in an ileostomy site is rare but has been recorded in patients with long-standing ileostomies after colectomy for chronic inflammatory bowel disease, as in this patient. Neuroendocrine carcinoma developing in this setting apparently has not been described before, however.