Activity of the morpholino anthracycline 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming unitsin vitro

Summary In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 g/ml either for 1 hour (201 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19%in vitro response at 0.05 g/ml and 69% at 0.5 g/ml) than with 1-hour exposure (1.3% at 0.05 g/ml and 12% at 0.5 g/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 g/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity in patients with those tumors.     

Assessment of primary health care access status: an analytic technique for decision making

Access to health care is an issue that has caught the attention of health care providers, policy formulators, and policy analysts, with particular emphasis on access to primary care, which affords all people a viable portal into the health care system.This paper proposes an analytical approach to the assessment of relative primary care access status, measured as the capability to deliver basic primary care services within specific geographic civil areas, or parishes, within the state of Louisiana. An additive multiattribute utility method is employed to develop a scoring system to rank parishes according to a primary care access, or health system capability, numerical score. Routinely collected parameters are used to measure each parish's current capability to provide primary care services. These parameters include demographic, mortality, morbidity, and resource data.A group of experts was used to give weight to each parish's parameter values, resulting in a relative score for each. Thus, parishes (or other geographic areas) can be ranked according to their primary care access status. This information can then be used to allocate resources, to distribute funds for health care services, and to guide policy formulation and implementation.     

Immunophenotypic and DNA content characteristics of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance

In the present paper we review the immunophenotypic characteristics of plasma cells (PC) and the PC DNA contents from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), and its value for the differential diagnosis between both entities. The strong reactivity for CD38 and the positivity for CD138 are the two best markers for identifying PC. Myelomatous PC display an heterogeneous phenotype consistent with the fact that the neoplastic clone is able to undergo a certain degree of differentiation. In addition, PC from MM patients usually lack surface expression of B-cell associated antigens and frequently display reactivity for markers which are not restricted to the B-cell lineage. In MGUS patients, two clearly defined and distinct PC subpopulations can be identified. One of these PC subpopulations shows phenotypic characteristics identical to those of normal PC, including a very strong reactivity for the CD38 antigen, intermediate/low light scatter characteristics and positivity for CD19, in the absence of CD56, and corresponds to the residual normal bone marrow PC. The second PC subpopulation shows an immunophenotype similar to that of myelomatous PC, characterized by a slightly lower reactivity for CD38 and strong CD56 expression, on the absence of positivity for CD19, these PC corresponding to the clonal counterpart. Using a simultaneous staining for PC and DNA, around 60% of MM and 73% of MGUS patients display DNA aneuploidy, the majority of them being hyperdiploid. However, in contrast to MM patients, in MGUS patients two clearly different PC subsets can be discriminated in most cases (73%): a diploid and an aneuploid (hyperdiploid) subset, corresponding to normal and clonal PC, respectively. Upon comparing hyperdiploid with diploid patients in MM, the former display a better prognosis, in line with the higher incidence of DNA hyperdiploidy in MGUS. A clear correlation between the percentage of S-phase PC and several prognosis features of MM has been found. In spite of these findings, no significant differences in the percentage of pathological S-phase PC are detected between MM and MGUS patients. Regarding the differential diagnosis between MGUS and MM, multivariate analysis shows that the ratio between the number of clonal and normal residual PC is the best single parameter.     

Coinfections by HIV, hepatitis B and hepatitis C in imprisoned injecting drug users

In order to know the prevalence and risk factors for coinfections by human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among injecting drug users (IDUs), a cross-sectional study was carried out in two prisons of the province of Cantabria, northern Spain. Three hundred and sixty-two IDU inmates were recruited. All inmates were interviewed and their blood tested for HIV, HBV and HCV. Crude and multiple risk factor adjusted for (by polychotomous logistic regression) odds ratios were calculated. Prevalence of HBV-HCV coinfection (42.5%) was higher than HIV-HBV-HCV coinfection (37.3%), whereas monoinfections were very uncommon (overall: 13%). Long-term injectors and reincarceration were the foremost risk factors for both coinfections, showing a trend between the degree of association and the number of viruses infecting a patient. No significant relationship between coinfection status and sexual practices was observed. The results related to coinfections are consistent with previous studies of prevalence and risk factors for HIV, HBV and HCV, in indicating that the high rates of coinfections among IDU inmates emphasise the need to harm-reduction policy across prisons in Spain.     

Unhealthy eating behaviour in adolescents

In recent years, eating disorders (Anorexia and Bulimia Nervosa) have increased and are appearing at increasingly younger ages. They affect predominantly adolescent females 12 to 25 years of age. The objective of this study of adolescents is to detect and discuss unhealthy eating behaviour, defined by either of two factors: (1) following a slimming diet not advised or supervised by any person trained in health care; or (2) eating very large quantities at irregular times, not related to anxiety or stress. A transversal study has been undertaken of 630 school children of 14–18 years of age (average: 15.9 years) in Cádiz (Andalucia, Spain), using an anonymous self-reporting questionnaire to collect data on personal and educational situation, on eating habits, on nutritive intake and knowledge of nutrition, and on dieting and physical exercise. The study has considered averages, ratios, statistical significance (x ²) and, as a measure of risk, the Disequality Ratio of Prevalence (DRP). Anomalous eating behaviour was detected in 46.3% (292), with females predominant by a ratio of 2:1. Comparing groups with anomalous and with normal eating habits, significant differences were detected in respect of: perception of body image (p<0.001), frequency of weighing oneself (p<0.05), periods of abstinence from eating (DRP 1.66; 95% confidence interval (CI): 1.66–2.37), provocation of vomiting (DRP 2.02; 95% CI: 1.13–3.65), use of laxatives (DRP 4.25; 95% CI: 1.08–9.63), and the exclusion of certain meals and types of food, mainly bread and cereals, fats and sugars. Conclusions are drawn on the substantial scale of unhealthy eating behaviour among adolescents in Cadiz. More adequate education on personal health and related social issues should be provided.     

Effects of selective phosphodiesterase inhibitors on platelet-activating factor- and antigen-induced airway hyperreactivity, eosinophil accumulation, and microvascular leakage in guinea pigs

There is currently interest in the potential use of selective inhibitors of cyclic nucleotide phosphodiesterases (PDE) in the treatment of asthma. In this study we examined the effects of three selective PDE inhibitors, milrinone (PDE III), rolipram (PDE IV) and zaprinast (PDE V), on the broncoconstriction produced by antigen and histamine, the airway hyperreactivity and microvascular leakage after aerosol exposure to platelet-activating factor (PAF) and antigen, and the antigen-induced eosinophil infiltration in guinea-pig lung. Inhaled rolipram (0.01–10 mg ml^–1) inhibited dose dependently the bronchospasm produced by aerosol antigen (5 mg ml^–1) an anaesthetised, ventilated guinea-pigs. Rolipram (10 mg ml^–1) produced maximal inhibition of antigen-induced bronchoconstriction but only partial inhibition of the response to aerosol histamine (1 mg ml^–1). Milrinone and zaprinast (each 10 mg ml^–1) showed weak, or no, inhibitory effects against bronchoconstriction produced by aerosol antigen or histamine. Pretreatment with rolipram (10 mg kg^–1, i.p.) prevented airway hyperreactivity to histamine which develops 24 h after exposure of conscious guinea-pigs to aerosol PAF (500 g ml^–1) or antigen (5 mg ml^–1). The pulmonary eosinophil infiltration obtained with 24 h of antigen-exposure was inhibited by rolipram. In contrast, milrinone and zaprinast (each 10 mg kg^–1, i.p.) failed to reduce either the airway hyperreactivity of the eosinophil accumulation in these animals. Rolipram (1–10 mg ml^–1) reduced the extravasation of Evans blue after aerosol PAF (500 g ml^–1) at all airway levels while a lower dose (0.1 mg ml^–1) was only effective at intrapulmonary airways. Rolipram (0.01–1 mg ml^–1) markedly reduced airway extravasation produced by inhaled antigen (5 mg ml^–1). Zaprinast (1–10 mg ml^–1) was also effective against airway microvascular leakage produced by aerosol PAF or antigen while milrinone (10 mg ml^–1) had no antiexudative effect. These data support previous suggestions that pharmacological inhibition of PDE IV results in anti-spasmogenic and anti-inflammatory effects in the airways and may be useful in the treatment of asthma.     

Hypotension induced by sodium nitroprusside administered via an automatic-adaptive dose regulating system. Experimental development

Sodium nitroprusside (NPS) is a potent vasodilator which is frequently administered for the control of arterial blood pressure and peripheral resistances. Manual regulation of the dose is difficult and requires a permanent surveillance of patients under treatment. Several attempts have been made to develop an automatized system able to safely control the dose of the drug in clinical practice. However, since now the results have not been completely satisfactory. The aim of our study was to develop of a new automatic-adaptative system able to continuously control the dose of NPS. The system consists of a high precision infusion pump controlled by a microprocessor. Arterial blood pressure is continuously monitorized and according to its values NPS is automatically regulated to maintain blood pressure within a preselected range. A control "fuzzy logic" algorithm was used. We have assessed the efficacy, adaptability, and safeness of the system. The system was tested in 15 mongrel dogs. The protocol was divided into two parts. During the first part a 25% to 30% reduction in blood pressure from baseline values lasting for a period of 4 hours was attempted. The second part was devoted to test the adaptability of the control unit during induced unstable hemodynamic situations. Group I dogs were subjected to volume overload. Group II were treated with noradrenaline to increase blood pressure, and group III underwent a venous bleeding to produce arterial hypotension. Control of arterial blood pressure was achieved after a minimum of 5 min and a maximum of 19 min (mean values = 13.3 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Seasonal and geographical variation of organochlorine residues in birds from Northwest Mexico

Eight species of birds (129 individuals) were collected from three agricultural areas with long histories of pesticide use in northwestern Mexico. Plucked carcasses were analyzed for organochlorine (OC) pesticides and polychlorobiphenyls (PCBs). DDE was found in all of the samples and at higher levels than other OCs. Mean (geometric) DDE concentrations varied from 0.04 (g/g) ppm in mourning doves (Zenaida macroura) to 5.05 ppm in double-crested cormorants (Phalacrocorax auritus). Hexachlorocyclohexane (HCH) was detected in 95% of the samples, but at lower levels than DDE. Hexachlorobenzene (HCB) residues were detected more frequently in birds from Mexicali (62%, p < 0.05) than in those from Yaqui and Culiacan. HCH and HCB concentrations were significantly higher in birds from Mexicali during the winter than in the summer (p < 0.05), indicating accumulation of these compounds during that period. Other OCs such as DDT, DDD, dieldrin, oxychlordane, heptachlor epoxide, endosulfan, and endrin were found at lower levels and less frequently. PCBs (quantitated as Aroclor^® 1260) were found mostly in cattle egrets (Bubulcus ibis) and cormorants at the three locations. Overall, concentrations of OCs were higher for Mexicali than for Yaqui and Culiacan (p < 0.01). In a few cases, DDE levels were above those that might adversely affect birds.     

Beneficial effect of verapamil added to chronic ACE inhibitor treatment on renal function in hypertensive elderly patients

This study analysed the effect of low doses ofverapamil added to chronic treatment withangiotensin-converting enzyme (ACE) inhibitors onblood pressure and serum creatinine levels in eightelderly hypertensive patients who had a steadyincrease of serum creatinine while on ACE inhibitors.The study was performed in eight elderly hypertensivesubjects, five men and three women (mean age 70 ±2 years; systolic blood pressure 173 ± 4 mmHg; diastolic blood pressure 99 ± 1 mm Hg) andserum creatinine of 1.60 ± 0.27 mg/dl beforetreatment. During an average of 25 weeks, ACEinhibitors significantly reduced both systolic anddiastolic blood pressures, but serum creatinine levelswere increased over basal levels (0,68 ± 0,20 mg/dl, p < 0.05). During an average of 10 weeks,the addition of verapamil did not decrease bloodpressure further, but serum creatinine levels werereduced to baseline. Our study suggests that theaddition of verapamil to ACE inhibitors can reverseACE-induced increase in creatinine levels in elderlyhypertensive patients in whom this side effect isobserved. This revised version was published online in August 2006 with corrections to the Cover Date.