Vitamin D (soltriol), light, and reproduction

Evidence from autoradiographic studies with 1,25(OH)2-vitamin D3 (vitamin D, soltriol) labeled with tritium and from the literature indicates that the steroid hormone soltriol regulates and modulates reproductive processes in the female, as it does in the male. Nuclear receptors for soltriol have been discovered in the uterus, oviduct, ovary, mammary gland, placenta, and fetal membranes, as well as in the pituitary and hypothalamus. Soltriol is recognized as a transducer and hormonal messenger of sunlight, acting as a somatotropic activator and modulator of vital processes for the seasonal and estival adaptation of growth, development, and procreation. Its influence on calcium equilibrium is just one of its many functions to serve this goal. This article reviews experimental, clinical, and epidemiologic evidence that suggests the involvement of soltriol in the control of reproductive processes, noting its importance for the onset of puberty, fertility, pregnancy, lactation, and probably sexual behavior. Cooperative actions between soltriol and other steroid hormones, especially estradiol, are pointed out.     

Continuous wave ultrasound measure of neonatal cerebral blood flow

We report cerebral blood flow (CBF) values for healthy neonates in five gestational age categories for 9 single and 7 combination measures of continuous wave Doppler ultrasound. Combinations of measures, particularly those from the anterior cerebral artery with a 5.0 MgH probe, increased the reliability and validity. The most reliable and valid single measure was mean flow velocity from the anterior cerebral artery (5.0 MgH probe). CBF values were lower for neonates with respirator support than for neonates without respirator support. No significant differences were found in CBF measures between intubated neonates who developed IVH and intubated neonates who did not develop IVH. Neonates who were intubated and developed intraventricular hemorrhage (IVH) were treated more vigorously than those who were intubated and did not develop IVH. By day 6, neonates with IVH had a significantly higher mean pH, mean serum bicarbonate, and mean positive base balance.     

Kinetic studies of the binding of acridinecarboxamide topoisomerase poisons to DNA: implications for mode of binding of ligands with uncharged chromophores

We have used stopped-flow spectrophotometry and the sodium dodecyl sulfate sequestration technique to study the kinetics of dissociation of DNA complexes of the mixed topoisomerase I/II poison N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (termed DACA) and a range of related linear tricyclic carboxamides with neutral chromophores. Complexes of DACA and related acridine and phenazinecarboxamides bearing an N,N-dimethylaminoethyl side chain dissociate from calf thymus DNA by a kinetic pathway involving four discernible steps in a manner similar to complexes of N-[(2-dimethylamino)ethyl]-9-aminoacridine-4-carboxamide (termed 9-amino-DACA). We infer from these findings that the side chains of DACA, its phenazine homologue, and 9-amino-DACA make comparable interactions with the DNA base pairs. In the case of 9-amino-DACA, a selective topoisomerase II poison, these are known, by crystallographic analysis, to involve hydrogen-bonding interactions between the protonated dimethylammonium group of the side chain and the O6/N7 atoms of guanine and to include a bridging water molecule hydrogen bonded to the carboxamide group and a phosphate oxygen. By contrast, we find that other linear tricyclic carboxamides with neutral chromophores which lack a peri nitrogen atom and are biologically inactive dissociate from DNA by a different mechanism in which it appears their side chains fail to interact with guanine. We conclude that the ability of the carboxamide group to lie preferentially in the plane of the chromophore, so facilitating the dimethylammonium-guanine hydrogen bond and ensuring maintenance of the water-bridged carboxamide-phosphate interaction, is a critical requirement for antitumor activity among ligands of the linear tricyclic carboxamide class. However, unlike the situation for 9-amino-DACA, for ligands with uncharged chromophores containing peri nitrogen atoms such as DACA, this outcome is possible with the 4-carboxamide group rotated cis or trans with respect to the ring nitrogen. This difference may have relevance to the ability of DACA to be a dual poison of both topoisomerases I and II.     

Participant satisfaction with a school telehealth education program using interactive compressed video delivery methods in rural Arkansas

Socioeconomic and demographic factors can affect the impact of telehealth education programs that use interactive compressed video technology. This study assessed program satisfaction among participants in the University of Arkansas for Medical Sciences' School Telehealth Education Program delivered by interactive compressed video. Variables in the one-group posttest study were age, gender, ethnicity, education, community size, and program topics for years 1997-1999. The convenience sample included 3,319 participants in junior high and high schools. The School Telehealth Education Program provided information about health risks, disease prevention, health promotion, personal growth, and health sciences. Adolescents reported medium to high levels of satisfaction regarding program interest and quality. Significantly higher satisfaction was expressed for programs on muscular dystrophy, anatomy of the heart, and tobacco addiction (p < 0.001 to p = 0.003). Females, African Americans, and junior high school students reported significantly greater satisfaction (p < 0.001 to p = 0.005). High school students reported significantly greater satisfaction than junior high school students regarding the interactive video equipment (p = 0.011). White females (p = 0.025) and African American males (p = 0.004) in smaller, rural communities reported higher satisfaction than White males. The School Telehealth Education Program, delivered by interactive compressed video, promoted program satisfaction among rural and minority populations and among junior high and high school students. Effective program methods included an emphasis on participants' learning needs, increasing access in rural areas among ethnic groups, speaker communication, and clarity of the program presentation.     

Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis

OBJECT: The object of this study was to compare the cost-effectiveness of intrathecal drug therapy (IDT) with that of conventional pain therapy (CPT) in patients suffering from chronic low back pain caused by failed back syndrome. In this study, the authors tabulated actual costs, in Canadian dollars, in a consecutive series of patients undergoing IDT within the Canadian health care system and have compared them with costs in a control group in the same environment. The influence of these treatments on the quality of life (QOL) was also analyzed. METHODS: The authors report on a series of 67 patients suffering from failed back syndrome, 23 of whom underwent implantation of a programmable drug delivery pump and 44 of whom acted as controls. Patients were followed for a 5-year period during which the investigators tabulated the actual costs incurred for diagnostic imaging, professional fees, implantation costs including hardware, nursing visits for maintenance of the pumps, alternative therapies, and hospitalization costs for breakthrough pain. From this data, cumulative costs for each group were calculated for a 5-year period. Patient responses on the Oswestry Pain Questionnaire were analyzed to assess the impact of treatment on QOL. The actual cumulative costs for IDT during a 5-year period were $29,410, as opposed to $38,000 for CPT. High initial costs of equipment required for IDT were recovered by 28 months. After this time point, managing patients with CPT became the more expensive treatment option for the remainder of the follow-up period. The Oswestry Disability Index showed a 27% improvement for patients in the IDT group, compared with a 12% improvement in the control group. CONCLUSIONS: In patients who respond to this treatment, IDT is cost effective in the long term despite high initial costs of implantable devices.     

An improved synthesis of 5,6-dimethylxanthenone-4-acetic acid (DMXAA)

5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is a novel anticancer agent with a number of unique activities, and is in clinical trial. The current synthesis of DMXAA involves six steps, beginning with a heterogeneous reaction to form an isonitrosoacetanilide, and gives an overall yield of 11% from 2,3-dimethylaniline. We report an alternative synthesis of the key intermediate 3,4-dimethylanthranilic acid via nitration of 3,4-dimethylbenzoic acid and separation of the key desired isomer by ready crystallisation. This, together with improvements in the rest of the synthesis, provide a shorter and higher-yielding route to DMXAA (22% overall from 3,4-dimethylbenzoic acid).     

Pathway-specific tumor suppression. Reduction of p27 accelerates gastrointestinal tumorigenesis in Apc mutant mice,but not in Smad3 mutant mice

Expression of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) is frequently reduced in human colorectal cancer, and this correlates with poor patient prognosis. To clarify the role of p27 in gastrointestinal (GI) cancer, we measured p27 expression, as well as the effect of germline deletion of p27, in 3 different mouse models of GI neoplasia. p27 expression was frequently reduced in GI tumors arising in 1,2-dimethylhydrazine (DMH) treated mice, and in Apc mutant Min/+ mice, but not in GI tumors arising in Smad3 mutant mice. Germline deletion of p27 resulted in accelerated tumor development and increased tumor cell proliferation in both DMH treated and Min/+ mice, but not in Smad3 mutant mice. p27 deficiency also led to increased adenoma to adenocarcinoma progression. These results indicate that reduction of p27 cooperates with mutations in Apc but not in Smad3 during GI tumorigenesis. Thus, tumor suppression by p27 is contingent on the specific oncogenic pathway that drives tumor development.     

Percutaneous imaging-guided core breast biopsy: 5 years' experience in a community hospital

OBJECTIVE: This study reports the results of a percutaneous imaging-guided core breast biopsy program in a community hospital. MATERIALS AND METHODS: We reviewed the prospectively collected results of our imaging-guided core biopsy program during its first 5 years (1994-1998). A total of 1333 lesions (94% of which were Breast Imaging Reporting and Data System (BI-RADS) assessment category 4) were sampled in 1183 patients. Patients with BI-RADS assessment category 5 lesions were referred to surgeons. Stereotactic guidance was used for the core biopsy of 506 lesions, and sonography was used to guide the predominantly 16-gauge needle core biopsy of 827 solid masses. RESULTS: One hundred forty-seven cancers were diagnosed in 1333 biopsies, resulting in a positive yield of 11%. Of 1020 patients with benign, concordant core biopsy results, 981 (96%) had at least one follow-up imaging examination within 36 months of the biopsy. Nineteen (2%) of these 1020 patients had a suspicious change at follow-up; 18 of these patients underwent surgical excision with benign findings. No cancers were found at imaging follow-up or by tumor registry linkage. All malignant core biopsy results were confirmed as malignant at surgical excision (positive predictive value 100%). Twenty-two patients with atypical ductal hyperplasia at core biopsy had subsequent surgery, and 12 (55%) of them were found to have cancer at surgery. CONCLUSION: An imaging-guided core biopsy program, developed and implemented by a small group of radiologists in a community hospital, can achieve successful results and provide an important service to patients and a cost-effective alternative to surgical biopsy. Our program emphasized sonographic guidance and achieved high follow-up compliance.