Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines

There is an increasing recognition that mitochondrial dysfunction is associated with autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction and how mitochondrial abnormalities might interact with other physiological disturbances such as oxidative stress. Reserve capacity is a measure of the ability of the mitochondria to respond to physiological stress. In this study, we demonstrate, for the first time, that lymphoblastoid cell lines (LCLs) derived from children with autistic disorder (AD) have an abnormal mitochondrial reserve capacity before and after exposure to reactive oxygen species (ROS). Ten (44%) of 22 AD LCLs exhibited abnormally high reserve capacity at baseline and a sharp depletion of reserve capacity when challenged with ROS. This depletion of reserve capacity was found to be directly related to an atypical simultaneous increase in both proton-leak respiration and adenosine triphosphate-linked respiration in response to increased ROS in this AD LCL subgroup. In this AD LCL subgroup, 48-hour pretreatment with N-acetylcysteine, a glutathione precursor, prevented these abnormalities and improved glutathione metabolism, suggesting a role for altered glutathione metabolism associated with this type of mitochondrial dysfunction. The results of this study suggest that a significant subgroup of AD children may have alterations in mitochondrial function, which could render them more vulnerable to a pro-oxidant microenvironment as well as intrinsic and extrinsic sources of ROS such as immune activation and pro-oxidant environmental toxins. These findings are consistent with the notion that AD is caused by a combination of genetic and environmental factors.     

Menstrual and reproductive characteristics and breast cancer risk by hormone receptor status and ethnicity: The Breast Cancer Etiology in Minorities study

We pooled multiethnic data from four population-based studies and examined associations of menstrual and reproductive characteristics with breast cancer (BC) risk by tumor hormone receptor (HR) status [defined by estrogen receptor (ER) and progesterone receptor (PR)]. We estimated odds ratios and 95% confidence intervals using multivariable logistic regression, stratified by age (<50, ≥50 years) and ethnicity, for 5,186 HR+ (ER+ or PR+) cases, 1,365 HR− (ER− and PR−) cases and 7,480 controls. For HR+ BC, later menarche and earlier menopause were associated with lower risk in non-Hispanic whites (NHWs) and Hispanics, and higher parity and longer breast-feeding were associated with lower risk in Hispanics and Asian Americans, and suggestively in NHWs. Positive associations with later first full-term pregnancy (FTP), longer interval between menarche and first FTP and shorter time since last FTP were limited to younger Hispanics and Asian Americans. Except for nulliparity, reproductive characteristics were not associated with risk in African Americans. For HR− BC, lower risk was associated with later menarche, except in African Americans and older Asian Americans and with longer breast-feeding in Hispanics and Asian Americans only. In younger African Americans, HR− BC risk associated with higher parity (≥3 vs. 1 FTP) was increased fourfold in women who never breast-fed, but not in those with a breast-feeding history, suggesting that breast-feeding may mitigate the adverse effect of higher parity in younger African American women. Further work needs to evaluate why menstrual and reproductive risk factors vary in importance according to age and ethnicity.     

Facial nerve management in patients with malignant skull base tumors

Journal of Neuro-Oncology - The course of the facial nerve through the cerebellopontine angle, temporal bone, and parotid gland puts the nerve at risk in cases of malignancy. In contrast to...     

The modified Kleinert splint in zone II flexor tendon injuries

The Kleinert controlled passive mobilisation splint has been modified to increase the passive range of motion of the proximal and distal interphalangeal joints to near normal. 12 fingers with complete divisions of both flexor tendons in Zone II treated by this method have been reviewed after six months. Nine regained full motion and two good motion while one, with an associated crush compound fracture of the proximal phalanx, had a poor result. The increased mobilisation did not adversely affect wound healing or associated repair of digital nerves.     

New discoveries and directions for medical, dental and dental hygiene research: low temperature atmospheric pressure plasma

Abstract:  The study of plasma integrates physics, chemistry, biology, and engineering, and has recently engaged medicine and dental hygiene in research efforts. The study of plasma holds promise for a myriad of applications ranging from lasers and electronics, hazardous waste management, decontamination, sterilization and disinfection of foods, soil, water, instruments, to medical uses in wound healing and treating certain types of tumours and cancers. Plasma represents a new state-of-the-art sterilization and disinfection treatment for certain oral and enviornmental pathogens, heat-sensitive materials, contaminated medical waste, hard and soft surfaces, and ventilation systems may assist health care facilities in the management of various health concerns. The role that Low Temperature Atmospheric Pressure Plasma (LTAPP) could play in the inactivation of pathogenic microorganisms might prove to be a new, faster, noncorrosive, more economical alternative, as well as support green healthcare.     

Obstetric antecedents for preterm delivery

OBJECTIVES: To investigate the obstetric antecedents for preterm delivery (PTD) in an Irish urban obstetric population, and to evaluate the incidence and outcome of such deliveries. STUDY DESIGN: A retrospective observational study of all preterm deliveries at the Rotunda Hospital, Dublin during the six-year period 1997-2002. The findings for early preterm deliveries (EPTD) (24+0-31+6 weeks' gestation), and late preterm deliveries (LPTD) (32+0-36+6 weeks' gestation) were analyzed separately. RESULTS: There were 38,795 deliveries after 24 weeks' gestation or >500 g birth weight, of which 2839 (7.3%) were preterm. Of all preterm deliveries, 626 (22.1%) were EPTD and 2213 (77.9%) were LPTD, resulting in an EPTD rate of 1.6% and an LPTD rate of 5.7%. Spontaneous unexplained preterm delivery accounted for 1221 (43.0%) of preterm deliveries (PTD), and of these 213 (34%) cases were EPTD and 1008 (45.5%) LPTD. The other most frequently observed obstetric causative factors, in order of importance, were multiple gestation (676; 23.8% of PTD), hypertensive disorders of pregnancy (243; 8.6%), antepartum hemorrhage (194; 6.8%), stillbirth (105; 3.7%), intrauterine growth restriction (53; 1.9%) and preterm prelabor rupture of membranes+/-chorioamnionitis (32; 1.1%). There were 75 early neonatal deaths among infants born prematurely, plus 105 stillbirths, resulting in a perinatal mortality rate of 63 per 1000 for PTD (n=180), which on subsequent analysis was 158 per 1000 for EPTD (n=99) and 37 per 1000 for LPTD (n=81). CONCLUSIONS: These data outline the obstetric factors linked to preterm delivery within a recent Irish urban obstetric population. Spontaneous idiopathic preterm labor was the principle causative factor in 43% of all preterm deliveries, and represents the proportion of women for whom future therapeutic intervention may be of benefit.