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Sleep in schizophrenia patients and the effects of antipsychotic drugs.

Insomnia is a common feature in schizophrenia. However, it seldom is the predominant complaint. Nevertheless, severe insomnia is often seen during exacerbations of schizophrenia, and may actually precede the appearance of other symptoms of relapse. The sleep disturbances of either never-medicated or previously treated schizophrenia patients are characterized by a sleep-onset and maintenance insomnia. In addition, stage 4 sleep, slow wave sleep (stages 3 and 4), non-REM (NREM) sleep in minutes and REM latency are decreased. The atypical antipsychotics olanzapine, risperidone, and clozapine significantly increase total sleep time and stage 2 sleep. Moreover, olanzapine and risperidone enhance slow wave sleep. On the other hand, the typical antipsychotics haloperidol, thiothixene, and flupentixol significantly reduce stage 2 sleep latency and increase sleep efficiency. Future research should address: (1) the sleep patterns in subtypes of schizophrenia patients; (2) the role of neurotransmitters other than dopamine in the disruption of sleep in schizophrenia; (3) the functional alterations in CNS areas related to the pathophysiology of schizophrenia during NREM sleep and REM sleep (brain imaging studies); (4) the short-term, intermediate-term, and long-term effects of atypical antisychotics on sleep variables.

Antipsychotic Agents↗

Estimating the duration of latency and survival time of snails with schistosomiasis.

By means of techniques of analyses of survival data developed for cancer trials it is possible to study aspects of the natural history of the infection of schistosomiasis on the intermediate host of transmission, the snail. The simultaneous study of three response variables is largely based on a model of Lagakos (1976). When using this approach in the schistosomiasis setting it seems inappropriate to assume that one process, the duration of latency, follows an exponential distribution. Thus this stage is modified to follow a normal distribution and the derivatives required to obtain maximum-likelihood estimates and approximate variances of all parameters are provided. Simple graphical tools for assessing the validity of distributional assumptions in survival data are available from industrial research. The reader's attention is drawn to a paper by Nelson (1972). The relevance and application of these methods to the current problem are described in Section 4. In the event that the times to death of prepatent and patent snails do not follow exponential distributions as assumed in the primary model, a further modification is introduced to enable either or both to follow Weibull densities. Lastly it is possible to adapt both the primary model of Section Three and the modified model of Section Five to allow for the inclusion of auxiliary variables or covariates. Again the required derivatives to obtain maximum likelihood estimates and approximate variances are provided.

Animals↗

Carotene, tocopherol, and ascorbate contents in subspecies of Brassica oleracea.

Cruciferous vegetables contain high levels of vitamins that can act as antioxidants, compounds that may protect against several degenerative diseases. The edible portions of 50 broccoli and 13 cabbage, kale, cauliflower, and Brussels sprouts accessions were assayed to determine variation in alpha-carotene, beta-carotene, alpha-tocopherol, gamma-tocopherol, and ascorbate contents within and between subspecies of Brassica oleracea. Ascorbate content was estimated in fresh samples using HPLC. Tissues for carotene and tocopherol analysis were lyophilized prior to extraction. Carotene and tocopherol concentrations were simultaneously measured using a reverse phase HPLC system. Results indicate that there is substantial variation both within and between subspecies. Kale had the highest levels of vitamins, followed by broccoli and Brussels sprouts with intermediate levels and then by cabbage and cauliflower, with comparatively low concentrations. Variability in vitamin content among the broccoli accessions suggests that potential health benefits that accrue with consumption are genotype dependent.

Antioxidants↗

Assessing the effect of intranasal steroids on growth.

Several studies have evaluated the effects of childhood use of corticosteroids on growth. In short-term studies, the budesonide (BUD) metered dose inhaler and methylprednisolone (injection) had significant effects on lower-leg growth, whereas terfenadine did not. When two doses of BUD (nasal inhaler, 200 or 400 microg once daily) were compared with placebo, only the 400-microg dose had a significant effect on short-term growth. Intranasal mometasone furoate (MF) (100 and 200 microg) had no significant effect on short-term lower-leg growth. In intermediate studies of 1-year duration, intranasal beclomethasone dipropionate (84 microg twice daily) significantly affected growth rate, whereas in a separate study, 100 microg intranasal MF once daily did not. Long-term growth data come from retrospective studies of children with asthma. In these studies, no significant effect on growth has been demonstrated in children taking inhaled beclomethasone dipropionate or BUD. The reason for the discrepancy between intermediate and long-term studies is unclear and warrants further study. Variables in childhood growth including seasonal variations may make growth difficult to assess. However, because growth suppression has been reported in children receiving inhaled or intranasal corticosteroids, the lowest effective dose of drug with a low systemic absorption ratio should always be used. Overall, there appears to be no growth suppression with 100 microg intranasal MF used once daily in children.

Administration, Intranasal↗

Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B-cells.

We have used a special class of human acute lymphocytic leukemias, the common "non-T/non-B" cell type, to define a hierarchy of genetic rearrangements that occur during the earliest stages of B-cell maturation. This has allowed us to identify intermediate cells predicted by a hierarchial model in which immunoglobulin heavy chain variable region gene formation precedes that of light chain and in which kappa light chain gene formation precedes that of lambda. The model emphasizes the flexible nature of immunoglobulin gene recombination that not infrequently produces aberrant or null genes that are phenotypically excluded from expression. Remaining alleles or isotypic genes can then be utilized as "spares" undergoing recombination until a valid gene is formed. Significantly, the excluded allele or isotype is frequently deleted from the genome. In addition to defining a pathway of genetic maturation, this analysis provides a powerful means to further classify cases of non-T/non-B-cell acute lymphocytic leukemia, most of which seem to reside at early stages along the B-cell pathway of differentiation.

DNA Restriction Enzymes↗

Permeability changes in hepatic mitochondria and altered glucose and urea metabolism in aroclor 1254-treated rats.

The influence of Aroclor 1254 (ARO) treatment or pair-feeding (PF) on gluconeogenesis and urea synthesis and on isolated hepatic mitochondria was studied in rats of different ages. ARO (300 mg/kg, po on 4 consecutive days) induced variable weight loss in young (153 +/- 10 g (initial wt), -10.9%), intermediate-age (195 +/- 10 g, -17.0%), and old (232 +/- 23 g, -4.9%) rats. Isolated mitochondria contained equal amounts of cytochromes aa3, b, c1 and c with exception that c1 and c were lower in the young ARO rats than in the PF controls. Mitochondria from ARO rats, which lost more weight than ad libitum-fed (AF) rats, showed suppression of ADP-stimulated H+ and oxygen uptake and succinate plus valinomycin maximal swelling in a potassium acetate and sucrose medium. Mitochondria from young ARO rats absorbed less incident light than mitochondria from PF or AF rats. Maximally swollen mitochondria from intermediate-age ARO rats, contracted more rapidly with antimycin addition than those from PF or AF controls. These findings showed greater permeability of ARO mitochondria to impermeable and accumulated ions. In contrast, mitochondria from ARO rats without significant weight loss showed activation of ADP-stimulated H+ and oxygen uptake and maximal swelling in comparison to mitochondria from AF and PF rats, but contracted like these controls after the antimycin addition. Urea synthesis in ARO rats, which lost 9.9% of initial body wt (173 +/- 6 g) and experienced a nitrogen deficit (Ebner et al., 1986), was significantly increased 12 min postinjection of NH4 acetate, and was greater than the urea level in AF rats at this time point. In comparison, gluconeogenesis was significantly increased in AF rats 12 min postinjection of NH4 acetate and was greater than in ARO rats at this time point. These differences were also observed when the data were expressed as the rate of glucose or urea appearance in peripheral blood per 100 g body wt. In PF rats, blood glucose and urea concentrations were intermediate to and indistinguishable from the ARO and AF groups. These data demonstrate that hepatic mitochondria from ARO rats that experienced a significant loss of body weight were suppressed and more permeable to ions than AF and PF controls. These mitochondrial properties may have predisposed the ARO rats toward urea formation rather than glucose synthesis and nitrogen retention.

Ammonia↗

Localization of transforming growth factor alpha in the human placenta and decidua: role in trophoblast growth.

Transforming growth factor alpha (TGF alpha) is an important growth regulatory molecule, the location and function of which at the human fetomaternal interface remain to be determined. The present study examined the presence of TGF alpha in the human placenta, decidua, and fetal membranes throughout gestation (from a total of 29 subjects) as well as its functional role in the proliferation of first trimester trophoblasts. The peptide was localized immunocytochemically with a monoclonal anti-TGF alpha antibody (Ab) (MF9) on paraffin-embedded tissues via the avidin-biotin complex-peroxidase technique with diaminobenzidine (DAB) as the chromogen. Omission or TGF alpha absorption of the primary Ab served as negative controls. Specific (cytoplasmic) staining was noted in typical stromal-type decidual cells, including cells of the decidua basalis and parietalis and chorionic decidua, throughout gestation. Villous trophoblast cells (syncytiotrophoblast and to a minor extent cytotrophoblast) at all gestational ages as well as extravillous cytotrophoblast cells (intermediate and cytotrophoblastic shell) also showed specific cytoplasmic staining. Chorionic trophoblasts showed variable staining, and little or no immunoreactivity was seen in the amniocytes. Second-passage first trimester human trophoblast cells (characterized by their expression of cytokeratin as well as other markers) were cultured in the presence of TGF alpha or neutralizing anti-TGF alpha Ab (TAb-1) or no additive for 18 h prior to exposure to 3H-TdR for 6 h to measure 3H-TdR uptake. TGF alpha (0-100 ng/ml) caused a dose-dependent stimulation of proliferation, reaching a near plateau at 6-100 ng/ml to slightly more than double the basal level. The presence of anti-TGF alpha Ab alone (25 micrograms/ml) did not significantly influence the proliferation of the cells, indicating the absence of significant endogenous TGF alpha in these cultures; however, the Ab was able to abolish the stimulatory function of exogenous TGF alpha. Exogenous TGF alpha also increased the number of trophoblast nuclei immunoreactive for proliferating cell nuclear antigen and reduced the incidence of multinucleate cells in culture. These results indicate that TGF alpha is present in the cells of the fetomaternal interface throughout human gestation and may function as a stimulator of trophoblastic growth in situ.

Cell Division↗

Is hypoglycaemia a marker for increased long-term mortality risk in patients with coronary artery disease? An 8-year follow-up.

BACKGROUND: No information is available regarding the association between low plasma glucose levels and cause-specific and all-cause mortality in patients with coronary artery disease (CAD). We aimed to investigate the relationship between hypoglycaemia and all-cause, cardiovascular and cancer mortality in a large population of patients with CAD. DESIGN: Patients were recruited from the BIP (Bezafibrate Infarction Prevention) registry, a secondary prevention prospective multicentre randomized, placebo-controlled, double-blind trial aimed to assess the efficacy of bezafibrate in reduction of coronary events. METHODS: The study included 14,670 CAD patients aged 45-74, divided into six groups: (1) hypoglycaemic (up to 69 mg/dl); (2) low normal (70-79 mg/dl); (3) euglycaemic (80-109 mg/dl); (4) impaired fasting glucose (IFG) (110-125 mg/dl); (5) borderline diabetics (126-139 mg/dl); (6) diabetics (> or 140 mg/dl). RESULTS: Patients comprised 131 with hypoglycaemia (0.9%), 731 with low normal glucose (5%), 9308 euglycaemic (63.4%), 1577 with IFG (10.7%), 617 borderline diabetics (4.2%) and 2306 diabetics (15.7%). Over a mean 8-year follow-up, crude all-cause mortality was higher in both diabetic (31.8%) and hypoglycaemic groups (25.2%) as compared with euglycaemics (14.9%; P<0.0001); CAD mortality was higher in diabetic and borderline groups (17.8 and 13.3%, respectively, versus 7.9% in euglycaemics; P<0.0001). The highest prevalence of cancer mortality was documented in the hypoglycaemic group (6.1 versus 2.9% in euglycaemics; P<0.02). Actuarial survival curves showed the lowest mortality in euglycaemic and low normal groups; the highest was seen in diabetic and hypoglycaemic patients. Intermediate values were found in borderline and IFG patients. After adjustment for variables, a significantly higher mortality rate was seen in hypoglycaemics when compared with euglycaemics (P<0.0001). Hypoglycaemia was identified as a predictor of increased all-cause and cancer mortality with a hazard ratio (HR) of 1.84 [95% confidence interval (CI) 1.29-2.61] and 2.26 (95% CI 1.12-4.57), respectively, but not of increased CAD mortality, with HR 1.30 (95% CI 0.73-2.29). CONCLUSIONS: Over a mean 8-year follow-up, hypoglycaemia emerges as a marker for substantially increased all-cause and cancer mortality among patients with CAD presenting with low fasting glucose levels.

Aged↗

Characterization of "Candidatus piscichlamydia salmonis" (order Chlamydiales), a chlamydia-like bacterium associated with epitheliocystis in farmed Atlantic salmon (Salmo salar).

To characterize intracellular gram-negative bacteria associated with epitheliocystis in farmed Atlantic salmon (Salmo salar), gills with proliferative lesions were collected for histopathology, conventional transmission and immunoelectron microscopy, in situ hybridization, and DNA extraction during epitheliocystis outbreaks in Ireland and Norway in 1999 and 2000, respectively, and compared by ultrastructure and immunoreactivity to nonproliferative gills from Ireland archived in 1995. Genomic DNA from proliferative gills was used to amplify 16S ribosomal DNA (rDNA) for molecular phylogenetic analyses. Epitheliocystis inclusions from proliferative gills possessed variably elongate reticulate bodies, examples of binary fission, and vacuolated and nonvacuolated intermediate bodies, whereas inclusions in nonproliferative gills had typical chlamydial developmental stages plus distinctive head-and-tail cells. Immunogold processing using anti-chlamydial lipopolysaccharide antibody labeled reticulate bodies from proliferative and nonproliferative gills. 16S rDNA amplified directly from Irish (1999) and Norwegian (2000) gill samples demonstrated 99% nucleotide identity, and riboprobes transcribed from cloned near-full-length 16S rDNA amplicons from Norwegian gills hybridized with inclusions in proliferative lesions from Irish (1999) and Norwegian (2000) sections. A 1,487-bp consensus 16S rRNA gene sequence representing the chlamydia-like bacterium (CLB) from proliferative gills had the highest percent nucleotide identity with endosymbionts of Acanthamoeba spp. (order Chlamydiales). Molecular phylogenetic relationships inferred from 16S rRNA gene sequences using distance and parsimony indicated that the CLB from proliferative gills branched with members of the order Chlamydiales. "Candidatus Piscichlamydia salmonis" is proposed for the CLB associated with epitheliocystis from proliferative gills of Atlantic salmon, which exhibits developmental stages different from those identified in nonproliferative gills.

Animals↗

Isthmic spondylolysis of the lumbar spine: MR imaging at 1.5 T.

The appearance on magnetic resonance (MR) images of the normal pars interarticularis in 13 patients was reviewed and contrasted with that of the pars in eight patients with spondylolysis. The pars defect usually had an intermediate signal intensity with all pulse sequences; however, this intensity was somewhat variable depending on the exact ratio of cartilage, fat, and fluid within each bone defect. The pars defect was best seen with spin-echo 600/20 (repetition time msec/echo time msec) images. In three cases, out-of-phase images showed the spondylolysis best, because of extension of fat to the borders of the defect. The sagittal view allowed one to separate spondylolysis from the joint space of posterior facets since the orientation of the defects is perpendicular to the facets; thus, a common pitfall encountered with cross-sectional axial imaging techniques is avoided. MR imaging poorly delineated bone fragments around the defect, which may produce nerve root impingement, but revealed other numerous complications that occur with spondylolysis, including spondylolisthesis and herniation of the disk above.

Adult↗

Pediatric choroid plexus neoplasms: MR, CT, and pathologic correlation.

Choroid plexus papillomas are rare, constituting approximately 0.5% of all intracranial neoplasms. Four benign choroid plexus papillomas and one choroid plexus carcinoma were retrospectively reviewed in patients aged 4-20 months who had been examined with magnetic resonance (MR) imaging with a field strength of 0.5 T or 1.0 T and with computed tomography (CT) before and after the administration of contrast material. In general, the tumors were of intermediate signal intensity on T1-weighted images and of either intermediate or increased signal intensity (T2 lengthening) with T2 weighting. All demonstrated variable areas of internal signal void interpreted as signifying regional blood flow, calcification, or old hemorrhage. CT findings included relatively uniform contrast enhancement. Microscopic pathologic changes of the benign lesions mimicked the appearance of normal choroid plexus and confirmed the highly vascular nature of these tumors. MR imaging, with its high-resolution multiplanar techniques, offers direct visualization of these lesions in relation to normal anatomy and better discrimination and confirmation of their intraventricular location, facilitating surgery and postoperative follow-up.

Carcinoma↗

Ultrastructural nasal pathology in children chronically and sequentially exposed to air pollutants.

Southwest Metropolitan Mexico City (SWMMC) children are repeatedly exposed to a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Nasal biopsies taken from these children exhibit a wide range of histopathologic alterations: marked changes in ciliated and goblet cell populations, basal cell hyperplasia, squamous metaplasia, and mild dysplasias. We studied the ultrastructural features of 15 nasal biopsies obtained from clinically healthy children 4 to 15 yr of age, growing up in SWMMC. The results were compared with nasal biopsies from 11 children growing up in Veracruz and exposed to low pollutant levels. Ultrathin sections of nasal biopsies revealed an unremarkable mucociliary epithelium in control children, whereas SWMMC children showed an epithelium comprised of variable numbers of basal, ciliated, goblet, and squamous metaplastic as well as intermediate cells. Nascent ciliated cells, as evidenced by the presence of migratory kinetosomes, were common, as were ciliary abnormalities, including absent central microtubules, supernumerary central and peripheral tubules, ciliary microtubular discontinuities, and compound cilia. Dyskinesia associated with these abnormal cilia was suggested by the altered orientation of the central microtubules in closely adjacent cilia. A transudate was evident between epithelial cells, suggesting potential deficiencies in epithelial junction integrity. Particulate matter was present in heterolysosomal bodies in epithelial cells and it was also deposited in intercellular spaces. The severe structural alteration of the nasal epithelium together with the prominent acquired ciliary defects are likely the result of chronic airway injury in which ozone, particulate matter, and aldehydes are thought to play a crucial role. The nasal epithelium in SWMMC children is fundamentally disordered, and their mucociliary defense mechanisms are no longer intact. A compromised nasal epithelium has less ability to protect the lower respiratory tract and may potentially leave the distal acinar airways more vulnerable to reactive gases. Impairment of mucociliary clearance has the potential to increase the contact time between deposited mutagenic particulate matter and the epithelial surface, thus increasing the risk for nasal carcinogenesis. Chronic exposures to air pollutants affect the whole respiratory tract; the nasal epithelium is an accessible and valuable sentinel to monitor exposures to toxic or carcinogenic substances.

Adolescent↗

Possible role of cytochromes P450 in lupus erythematosus and related disorders.

Cytochromes P450 comprise a superfamily of enzymes pivotal in the metabolism of innumerable substrates of both endogenous and exogenous origin. The total number of distinct P450 genes, each encoding a different enzyme in humans, is estimated to be at least 60 and possibly several hundred. The cytochrome P450 (CYP) superfamily nomenclature system is based on divergent evolution of the genes. Most of the enzymes within gene families CYP1, CYP2, CYP3 and CYP4 appear to have evolved as the body's primary defense against the onslaught of chemicals confronted on a daily basis. Whereas P450 enzymes more than 3.5 billion years ago were undoubtedly designed as necessary components of signal transduction pathways, in the past billion years most P450 enzymes have become generally responsible for the detoxification of numerous foreign chemicals. During such oxidative metabolism, it has become increasingly apparent that these enzymes are also capable of functioning in an ambivalent manner, generating toxic intermediates. More than a dozen human P450 polymorphisms have been characterized. Genetic variability in P450 expression is therefore likely to have significant bearing on individual susceptibility to chemical toxicity. In this review, genetic differences in human P450 expression are outlined, and their possible relationship to autoimmune disease is examined. In addition, the speculative role of P450 polymorphisms in several 'lupus-like' disorders is discussed.

Autoimmune Diseases↗

Cognitive, behavioral, and motor effects of the NMDA antagonist ketamine in Huntington's disease.

BACKGROUND: Excitotoxicity may contribute to neuronal degeneration in Huntington's disease (HD). N-methyl-D-aspartate (NMDA) receptor antagonists can prevent neuronal degeneration caused by excitotoxicity, but their effects in HD patients are not known. METHODS: We investigated the acute cognitive, behavioral, and motor effects of the NMDA-receptor antagonist ketamine in HD patients. Double-blind infusions of 0.10, 0.40, and 0.60 mg/kg/hr ketamine were given to 10 HD patients on one test day and compared with placebo infusions on a second, identical testing day. Linear mixed-effects models and randomization tests were used to identify whether, and at which dose, a significant change from baseline occurred in outcome variables. RESULTS: We demonstrated that ketamine is well tolerated at low and intermediate subanesthetic doses. Intermediate ketamine doses produced specific decline in memory and verbal fluency. Higher subanesthetic doses caused a significant increase in psychiatric symptoms and impairment of eye movements. CONCLUSIONS: These results describe the spectrum of clinical effects produced by increasing NMDA receptor blockade in HD patients. The clinical effects appearing with higher levels of NMDA receptor blockade can identify the range of doses used in clinical trials of NMDA receptor antagonists.

Adult↗

The role of diabetes duration, pubertal development and metabolic control in growth in children with type 1 diabetes mellitus.

OBJECTIVE: To investigate whether pubertal development, duration of type 1 diabetes mellitus (DM1), or metabolic control play some role in the anomalies in growth observed in diabetic children. PATIENTS: We conducted a prospective evaluation of 83 patients (37 female, 46 male) who were followed from the onset of DM1 at the prepubertal stage until they reached final height. All patients were treated with a conventional regimen of insulin. METHODS: Height SDS, weight SDS, BMI SDS, duration of DM1 in years, and values of HbA1c were the study variables. RESULTS: In prepubertal (P1) girls (data for the initial vs the intermediate evaluations): weight SDS was -0.14 +/- 0.19 vs 0.11 +/- 0.20, p = ns; BMI SDS -0.25 +/- 0.15 vs 0.01 +/- 0.13, p = ns. In postpubertal (P3) girls, weight SDS was 0.49 +/- 0.2 vs 1.2 +/- 0.32, p <0.01; BMI SDS 0.09 +/- 0.16 vs 1.03 +/- 0.24, p <0.01, whereas in P1 boys, height SDS was 0.16 +/- 0.30 vs -0.20 +/- 0.27, p <0.05; and in P3 boys: 0.09 +/- 0.21 vs -0.28 +/- 0.26, p <0.05. Thus pubertal development influenced changes observed in girls with DM1, but did not do so in boys. The anomalies described in children with DM1 were observed from the third year of DM1 duration in both girls and boys. We did not observe any correlation between HbA1c values with height SDS, weight SDS or BMI SDS. CONCLUSIONS: The anomalies in growth observed in girls with DM1 are related to pubertal development, but this is not the case in boys. Alterations in children with DM1 were found from the third year of DM1 duration. Furthermore, the present data also indicate that the degree of metabolic control observed in our patients treated with modern but conventional regimen did not play a major role in the anomalies observed.

Child↗

Long-term effects of accelerated or delayed sexual maturation on reproductive output in wild female house mice (Mus musculus).

The effects of acceleration and delay of puberty in female house mice on survival and reproduction were tested using 6 experimental groups: (1) control females mated at the time of first oestrus, (2) females mated at weaning, (3) females treated with male urine starting at weaning and mated at first oestrus, (4) females housed in groups and mated at first oestrus, (5) females housed alone, treated with urine from grouped females and mated at first oestrus, and (6) females housed alone and mated at 68 days of age. Females caged with males at weaning or treated with male urine and mated at puberty had lower rates of survival to 180 days of age, but did not differ in rates of fertility from mice in the other four treatments. Those females that were housed with males from weaning or treated with male urine also had smaller total numbers of litters, fewer total young, and smaller average litter sizes than did females for which the age of mating was delayed, by grouping or treatment with urine from grouped females, or by being held until age 68 days before mating. Control females mated at first oestrus generally were intermediate or did not differ from the male treatments on these dependent variables. There were no differences in the average number of female young/litter across the 6 treatments. However, females that were delayed in age of first mating had significantly more male young/litter than did females that were accelerated in their sexual development or control females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stomach cancer incidence in Brazil: an ecologic study with selected risk factors.

Contrary to many industrialized countries in which a sharp decline in stomach cancer incidence has been observed, Brazil still shows intermediate to high incidence rates. An ecologic analysis was performed to explore variables possibly associated with the development of stomach cancer. Cluster analysis, principal component analysis, and factor analysis were carried out with population data, including the following: stomach cancer incidence rates in the early 1990s obtained from population-based cancer registries in Porto Alegre, Campinas, Fortaleza, Belém, and Goiânia; and data from a Brazilian national survey on family expenditures (several diet consumption items and availability of home refrigerators) carried out in 1974-75. The results suggested that past availability of a home refrigerator, i.e. food preservation, may have played an important role in currently observed differences in stomach cancer incidence among the various populations studied in Brazil. Differences in living standards among populations in these cities also appear to have played an important role in the observed incidence differences.

Journal Article↗

Mathematical models of oxygen and carbon dioxide storage and transport: the acid-base chemistry of blood.

This article describes a mathematical model of the acid-base chemistry of blood. The model is formulated from first principles by considering the "components" of blood and the reaction equations in the plasma and erythrocyte fractions. Equations are formulated to describe the total concentration of blood components, the physicochemical properties, and the equilibrium position of reactions. The model includes 28 equations and 12 parameters. All equations can be solved from six variables included in the model. The model uses simple mathematics, without introducing intermediate concepts or linear coefficients necessary for algebraic solution. Model equations are solved simultaneously using numerical methods. Model parameters are estimated and the model verified for plasma, fully oxygenated blood, and deoxygenated blood. Published data are used to estimate model parameters and normal conditions and to verify model simulations. The model reproduces experimental results, including addition or removal of CO2, or strong acid to plasma; CO2, strong acid or haemoglobin to blood; and the effects of deoxygenating blood. The model can also be used as the basis for models of whole body CO2 transport as illustrated in the accompanying article. As such, it is possible to simulate the effects on blood of physiological changes in ventilation or metabolism.

Acid-Base Equilibrium↗