A comparison of breast cancer secondary prevention activities and satisfaction with access and communication issues in women 50 and over.

BACKGROUND: Between 1950 and 1990, the incidence of breast cancer increased about 52% and the mortality rate increased 4%. Prevention programs (mammograms and clinical breast exams) can positively affect both cost control and mortality rates. Balancing the costs of preventive screening against the potential savings is a part of an ongoing debate centering on the age at which women should have yearly mammograms. Yet, if all agencies agree that women aged 50 and over should receive yearly mammograms, then why are so many women aged 50 and over not being screened? METHODS: Using previously validated instruments, this study surveyed residents of Spokane County, Washington. Respondents (1,850 returned of 2,600) were compared over time by demographic characteristics and by insurance type to identify any significant differences between those who had preventative screens and those who did not. Issues involving access to screening and communication with healthcare providers were also examined. RESULTS: Factors that affect whether women receive preventative screening include insurance type, provider type, long waiting times, and poor communication among the doctor, the staff, and the patient. CONCLUSION: The most important determinant to whether preventative screening is being conducted is the relationship between the patient and their healthcare provider.

In vivo and in vitro comparison of the short-term hematopoietic toxicity between hydroxyurea and trimidox or didox, novel ribonucleotide reductase inhibitors with potential anti-HIV-1 activity.

Inhibitors of the cellular enzyme ribonucleotide reductase (hydroxyurea, [HU]) have been proposed as a new therapeutic strategy for the treatment of HIV type-1 (HIV-1) infection. However, HU use may be limited by the frequent development of hematopoietic toxicity. We report here short-term hematopoietic toxicity in mice receiving HU when compared to either of two more potent enzyme inhibitors, didox (DX) and trimidox (TX). High dose HU, DX, and TX monotherapy (500, 460, and 220 mg/kg/day respectively) was administered by daily i.p. injection (Monday-Friday) to C57BL/6 mice for 10 weeks. Effects on hematopoiesis were established by quantitating peripheral blood indices (hematocrit, hemoglobin, mean corpuscular volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, RBC, and WBC) and numbers of colony-forming units-granulocyte-macrophage (CFU-GM) and BFU-E from bone marrow and spleen. HU produced rapid induction of a macrocytic hypochromic anemia and altered white blood cell kinetics associated with myelosuppression defined as reduced marrow organ cellularity and induction of splenic extramedullary hematopoiesis. Compared to HU, TX and DX induced fewer changes in peripheral blood indices and CFU-GM and BFU-E per hematopoietic organ. In vitro human and murine marrow CFU-GM and BFU-E colony formations were assayed in the presence of dose escalation HU, DX, or TX (0, 1, 10, 50, 100, and 200 microM). HU inhibited colony formation more than either DX or TX. These in vivo and in vitro studies suggest that novel ribonucleotide reductase inhibitors TX and DX may provide an effective alternative to HU in HIV-1 therapy because they demonstrate reduced hematopoietic toxicity.

Influence of lithium on the cellular environment.

In order to study the influence of lithium on the cellular environment, we conducted research in multiple experimental models: groups of rats with normal cerebral excitability and groups susceptible to audiogenic convulsion, rat neuroglia cultures and perfusion of dog isolated head. We assumed blood composition to be a good indicator of cell environment composition. Blood serotonin level differs in the two groups of animals. Lithium induces a decrease of blood serotonin and an increase of amine concentration in some of the cerebral regions of rats susceptible to audiogenic convulsions. Inverse effects occur in rats with normal cerebral excitability. In the perfused, isolated head of a dog, lithium immediately decreases blood serotonin level. Na and water have a diminished metabolization during the first 24 hrs. in both animal groups. Decrease in metabolization is somewhat greater in hyperexcitable animals. Within 48 hrs. after lithium injection, there is an increase of Na metabolization, probably determined by its storage in the interstice. Renal elimination of K decreases under the influence of lithium 48 hrs. after administering one dose of lithium. Lithium induces, immediately after injection, a decrease of blood Na concentration in the efferent flow of the jugular vein of a perfused dog head. When used in cell cultures, lithium (2 mM concentration) stimulates glial cells division (astrocytes, oligodendrocytes), increases their growth and aging rates. The effects of lithium may be due to its toxicity. Therefore, lithium alters the composition of the cellular environment depending on dose and on the state of the body.

Use of an international faculty/student exchange program as a process to establish and improve graduate education and research within an allied health discipline.

It has been recognized in the allied health professions that allied health disciplines must enhance and increase their research and scholarly activity. If faculty/staff are to be judged in the academic environment in which they work, their efforts to conduct research must be supported. Recognition for academic scholarship measured by the performance of research and scholarly activity is often difficult for faculty/staff to attain because of increased demands for scheduled time devoted to classroom instruction and student advising. This inability for faculty/staff to engage in research and scholarly activity often is enhanced by the lack of proper and adequate facilities and equipment. Also important is the role of graduate education, which itself, provides a stimulus for the performance of research and scholarly activity. This article reports outcomes achieved by an international faculty/staff-student program that provides an opportunity for faculty/staff and students within an allied health discipline to conduct research and scholarly activity. This program could serve as a model to identify the strengths and benefits that can be achieved by such programs. This program is capable of improving the research and scholarly activity of all academic units within an allied health discipline.

The effects of lithium in reversing hydroxyurea induced suppression of hematopoietic progenitor cells in vitro using retroviral infected long-term marrow cultures.

Lithium has been known for its ability to induce the production of hematopoietic cells following administration in vivo to minimize the toxic effects on hematopoiesis as a consequence of drug treatment. The drug hydroxyurea (HU), a ribonucleotide reductase inhibitor, has been used in the treatment of a variety of neoplastic and non-neoplastic diseases, such as cancer and sickle cell anaemia. Hydroxyurea has more recently been implicated for use in the treatment of acquired immunodeficiency syndrome (AIDS). However, its major limitations have been due to its toxicity. Hydroxyurea selectively inhibits DNA synthesis and due to its brief duration, the drug is only toxic to those cells which are selectively synthesizing DNA during the period of exposure. The most important of these toxicities, and which serves as a dose limiting factor in treatment, is the induction of bone marrow suppression. In this study we investigated the possible beneficial effects of administering lithium (LiCl) to murine leukemia virus (MuLV) infected and non-infected long term bone marrow cultures (LTBMC). These cultures were then treated with either 0.2 mM hydroxyurea, 1.0 mM LiCl, or a combination of both. Samples were collected from LTBMC supernatants at 1, 2, 3, 4, 5 and 6 weeks post-treatment. Culture supernatants were then monitored to observe their repopulation of hematopoietic progenitors. The results demonstrated the effects of lithium in restoring hydroxyurea suppressed numbers of myeloid (CFU-GM) progenitors to within a normal range and also in re-establishing erythroid (BFU-E) progenitors.

The effects of lithium gamma-linolenic acid in reversing LPBM5 MuLV induced suppression of hematopoietic progenitor cells in vitro.

Lithium gamma linolenic acid (Li-GLA), was evaluated for its possible role as an antiviral agent. Li-GLA 15 micrograms ml-1 was administered to both normal and LP-BM5 MuLV retroviral infected murine bone marrow cultures. After 2 weeks of treatment, numbers of progenitors being produced by infected/treated cultures were reduced to some 10% that of normal cultures. In the remaining 4 weeks, numbers of CFU-GM and BFU-E hematopoietic progenitors returned within normal range. The efficacy of Li-GLA in relieving retroviral hematopoietic bone marrow suppression correlates to a reduction in interleukin-4 (IL-4) secretion, normally elevated in association with LP-BMP5 infection. These data indicate that this reduction in bone marrow suppression of LP-BMP5 infected cells may be due to a killing of infected cells by the Li-GLA, rather than stimulating hematopoiesis as with other lithium compounds. To conclude this may indicate the possible dual effect of administration of LiGLA to virally infected individuals in reducing viral titre and to lower the toxicities associated with long term drug therapy.

Effective use of ribonucleotide reductase inhibitors (Didox and Trimidox) alone or in combination with didanosine (ddI) to suppress disease progression and increase survival in murine acquired immunodeficiency syndrome (MAIDS).

Ribonucleotide reductase inhibitors (RRIs) have been recently shown to inhibit retroviral replication. We examined a new series of RRIs, 3,4-dihydroxybenzohydroxamic acid (Didox) and 3,4,5-trihydroxybenzohydroxamidoxime (Trimidox) for their ability to alter disease progression in murine acquired immunodeficiency syndrome (MAIDS), both alone and in combination with 2',3'-dideoxyinosine (ddI). MAIDS disease was induced by inoculation of female C57BL/6 mice with the LP-BM5 murine leukemia virus (MuLV) and disease progression characterized by extensive peripheral lymphadenopathy and splenomegaly. Efficacy of treatment with these drugs was based upon their ability to influence survival and disease pathophysiology by monitoring the development of splenomegaly. Toxicity was determined by changes in body weight, total peripheral white blood cell count and hematocrit. Didox or trimidox monotherapy was associated with increased survival and decreased disease pathophysiology, with no apparent toxicity. Combined with ddI, their ability to reduce development of viral induced splenomegaly was enhanced compared to trimidox, didox or ddI alone. These results demonstrate RRIs have potent activity in reversing the disease manifestations characteristic of MAIDS. Further studies are warranted to determine human clinical efficacy.

Instant lithium monitoring: a clinical revolution in the making.

The recent availability of portable ion selective electrodes (ISE) for clinical applications has enabled lithium estimations to be performed instantly and at close proximity to patients. The significance of this is, not in the accuracy of the determination, but in the speed of the feedback provided to doctor and patient, and hence the promotion of compliance. The impact of this on lithium therapy can only be described as a clinical revolution in the making.

Effect of lithium in immunodeficiency: improved blood cell formation in mice with decreased hematopoiesis as the result of LP-BM5 MuLV infection.

Lithium salts have been demonstrated to induce the production of hematopoietic cells following administration in vivo and to minimize the reduction of these cells following treatment with either radiation, chemotherapeutic or antiviral drugs. We have previously demonstrated that lithium, when administered in vivo to immunodeficient mice infected with LP-BM5 MuLV (MAIDS) significantly reduced the development of lymphadenopathy, splenomegaly, and the lymphoma associated with late-stage immunodeficiency disease in this model, and increased the survival of these animals compared to virus-infected controls not receiving lithium. We report here the results of in vivo studies in the MAIDS model that determined the effect of lithium on peripheral blood indices and the number of myeloid (CFU-GM), erythroid (BFU-E) and megakaryocyte (CFU-Meg) hematopoietic progenitors from bone marrow and spleen harvested from immunodeficient mice receiving lithium carbonate (1 mM) placed in their drinking water compared to virus-infected controls not receiving lithium. Time-points evaluated were at weeks 1, 5, 9, 13, 17, and 21 postviral infection. Virus-control mice not receiving lithium demonstrated all the signs that are characteristic of MAIDS, i.e., splenomegaly, lymphadenopathy, hypergammaglobulinemia, reduced hematopoiesis, and death. Infected mice receiving lithium demonstrated diminished presence of splenomegaly, lymphadenopathy, hypergammaglobulinemia, no suppression of hematopoiesis nor mortality. Enhanced hematopoiesis was demonstrated by neutrophilia, lymphocytosis, thrombocytosis, and erythrocytosis that was evident by increased myeloid, erythroid, and megakaryocyte progenitor cells cultured from bone marrow and spleen. These studies further demonstrate that lithium influences the disease process in the MAIDS model and restricts the development of hematopoietic suppression that develops in this retroviral animal model of immunodeficiency.

Increased hematopoietic toxicity following administration of interferon-a with combination dideoxynucleoside therapy (zidovudine plus ddI) administered in normal mice.

Because of the urgency to develop drugs which will effectively combat HIV infection, many combination therapies which have proved effective against HIV in vitro have undergone, or are undergoing clinical trial. Unfortunately many of drugs are being used without rigorous and exhaustive preclinical evaluation to assess their potential to develop hematopoietic toxicity. We report here the results of two in vivo studies performed to analyze the effect of combined zidovudine (AZT) plus didanosine (ddI) therapy, either with or without interferon-a (IFN-a), on murine hematopoiesis. Normal C57BL/6 female mice were administered AZT (1.0 mg/ml) plus dose-escalation ddI (0.1, 1.0 and 2.5 mg/ml) placed in their drinking water. Control mice received IFN-å (100 units/ml) alone. Mice were serially bled and sacrificed over a six-week period for assessment of hematopoietic toxicity measured by peripheral blood indices and assays of hematopoietic progenitors, i.e., erythroid (BFU-E), myeloid (CFU-GM), and megakaryocyte (CFU-Meg) cultured from bone marrow and spleen. AZT plus dose-escalation ddI decreased the hematocrit and white blood cell count when administered to normal mice compared to untreated controls during the six-week examination period. Marrow derived BFU-E, CFU-GM, and CFU-Meg were all reduced, however an increase was observed from the spleen for all three progenitor cell types. Use of IFN-a, in addition to combination AZT plus ddI further decreased the hematocrit, white blood cells and platelets. Marrow derived CFU-GM and CFU-Meg were increased slightly and only marginally for BFU-E with a similar response observed from the spleen. These results demonstrate that combination AZT plus ddI when used in vivo may produce synergistic hematopoietic toxicity, and that the addition of IFN-a to this treatment regimen increases this toxicity. These data indicate caution when this therapeutic approach is suggested for patients infected with HIV. If used, these patients will require careful monitoring for blood cell toxicity.

Recovery of cellular activity in cryopreserved human foetal brain tissue.

Since long-term cryopreservation can cause losses in neural tissue viability and function a prerequisite would be the ability to monitor and promote functional recovery in donor tissue intended for neural transplantation. Rapid assessment of cryopreserved tissue's functional status prior to grafting is presently difficult in a clinical setting. A convenient indicator of functional status may be the level of DNA synthesis activity taking place in the tissue. Using immunocytochemical detection of incorporated bromodeox-yuridine we have quantified and compared DNA synthesis activity (expressed as proliferative capacity (PC)) in human foetal mesencephalic, striatal, cortical and cerebellar tissue before and after a 275-376 day storage in liquid nitrogen. There was a post-storage reduction in viability of 48-73% and in PC of 26-59%; the higher the PC before storage the greater the reduction after. Incubation of cryopreserved tissue with fetal calf serum resulted in 2-4-fold higher PC levels than serum-untreated controls and reached 80% of fresh tissue levels in mesencephalic cells after 3-4 h incubation. Assuming that quantification of proliferative activity is a practical indicator of the tissue's functional status, these findings suggest that treatment of the tissue with serum can largely restore the lost function caused by cryopreservation.

Magnesium and lithium antagonism of carbachol- and electrically-induced smooth muscle contractions in the rat gastrointestinal tract.

The pharmacological actions of lithium and magnesium have been investigated using isolated smooth muscle preparations from the rat gastrointestinal tract. Tissue contraction was evoked by means of carbachol or electrical field stimulation and the degree of inhibition of contraction caused by lithium was measured. Lithium effects were compared with those of the chemically similar ions, magnesium and calcium, by manipulation of the physiological buffer solutions. Lithium antagonism was enhanced when tissue contractile mechanisms were dependent on extracellular calcium concentration in the bathing fluid. This suggests that lithium is acting at the cell membrane by preventing calcium entry via ion channels. These results are consistent with evidence from clinical studies which indicate low cellular accumulation of lithium at therapeutic concentrations.

A pilot study of erythrocyte lithium-sodium countertransport in women during the menstrual cycle.

OBJECTIVE: The study investigated lithium-sodium countertransport in erythrocytes of normal female volunteers during different phases of the menstrual cycle or during administration of oral contraceptives. METHODS: Ten normally menstruating, and eight oral contraceptive using, normal female subjects were studied over at least one cycle. Erythrocyte lithium-sodium countertransport was determined using. standard, previously validated methods at different phases of the menstrual cycle. Hematological, electrolyte, blood pressure and other transport measures were also made and these were related to the self-reported incidence of premenstrual symptomatology. RESULTS: A correlation, (p < 0.02), was found between lithium-sodium countertransport rate and the premenstrual symptom severity score but only in the premenstrual phase. There was no correlation between any of the electrolyte, blood pressure or hematological data and lithium-sodium countertransport rate nor between it and other ion transport measures. Pre-menstrual symptomatology was conspicuously absent from those subjects taking oral contraceptives. Cyclical fluctuations in normally menstruating women, and differences between them and oral contraceptive users, were seen in lithium-sodium countertransport rate although the groups were too small to show statistical significance. CONCLUSIONS: Care was taken to exclude influences due to circadian, dietary and diurnal variations and the present results show somewhat less within-individual variability in erythrocyte lithium-sodium countertransport during the menstrual cycle than do other reports in the literature. Some interesting features were observed which justify a much larger scale study than the present pilot experiment which should involve a larger number of subjects studied over more than one cycle and in particular a more detailed study of the ovulatory phase.

Plasma magnesium levels in a population of psychiatric patients: correlations with symptoms.

Plasma magnesium levels were tested in a group of 155 psychiatric in-patients with a variety of diagnoses and were correlated with the severity of their symptoms. We hypothesized that lower Mg levels would correlate with a higher degree of anxiety, tiredness and other symptoms characteristic of Mg deficiency. No such correlations were observed. However, Mg levels varied widely, with 22.4% below, and 10.4% above the normal range. There was a strong association for more disturbed and excitable patients to have abnormal (either high or low) levels. We speculate that more disturbed patients might have some abnormality of Mg metabolism with possible therapeutic implications.

Magnesium inhibition of carbachol-induced contractions of the rat uterus and gastrointestinal tract: ex vivo effect of long term streptozotocin-induced diabetes.

Rats were rendered diabetic by a single administration of streptozotocin (STZ). They were maintained in the diabetic state for six weeks before being killed, and diabetic state was confirmed by routine urine and blood glucose estimations. The contractile sensitivity of jejunum, colon, stomach fundus and uterus to carbachol was reduced in control animals by increasing buffer magnesium concentration from 1.9 mmol/litre to 23.8 mmol/litre. This magnesium effect was reversed in the colon, stomach fundus and uterus of streptozotocin-diabetic animals, with contractile sensitivity being enhanced in the presence of increased magnesium concentration. In the jejunum, however, the magnesium effect was not reversed by STZ-induced diabetes. In diabetic animals, magnesium generally had the opposite effect on gastrointestinal and uterine tissues when compared with control animals. This suggests that, in the diabetic condition, any altered gastrointestinal function may be due to an underlying difference in the sensitivity to changes in magnesium.