Inflammatory breast cancer and body mass index

PURPOSE: No studies have investigated the etiology of inflammatory breast cancer (IBC), the most lethal form of breast cancer. Because high body mass index (BMI) is associated with decreased risk of premenopausal breast cancer but increased risk of postmenopausal breast cancer, we evaluated whether high BMI was a risk factor for IBC. PATIENTS AND METHODS: In a case-comparison study, we matched by ethnicity and registration date 68 IBC patients treated at The University of Texas M.D. Anderson Cancer Center from 1985 to 1996 with 143 patients with non-IBC and 134 patients with cancer at sites other than the breast or reproductive tract (non-breast cancer). The non-breast cancer group was used in lieu of a population-based, healthy control group, which was not available. RESULTS: IBC patients were younger at menarche and the time of their first live birth than non-IBC and non-breast cancer patients. The proportion of premenopausal IBC patients was higher than the proportion of premenopausal women in the comparison groups, although differences were not significant. There were no differences in height, but IBC patients were heavier (77.6 kg) than non-IBC (70.0 kg) and non-breast cancer patients (68.0 kg). After adjusting for other factors, women in the highest BMI tertile (BMI > 26.65 kg/m2) relative to the lowest tertile (BMI < 22.27) had significantly increased IBC risk (IBC v non-IBC, odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.05 to 5.73; IBC v non-breast cancer, OR = 4.52, 95% CI = 1.85 to 11.04). This association was not significantly modified by menopausal status and was independent of age at menarche, family history of breast cancer, gravidity, smoking status, and alcohol use. CONCLUSION: Our investigation showed that high BMI was significantly associated with an increased risk of IBC. This association did not vary by menopausal status, although IBC patients were more likely to be premenopausal. Confirming our findings and identifying other IBC risk factors may provide directions for future research on the aggressive nature of IBC.     

Effect of sympathectomy on mechanical properties of common carotid and femoral arteries

Sympathetic stimulation is accompanied by a reduction of arterial distensibility, but whether and to what extent elastic and muscle-type arterial mechanics is under tonic sympathetic restraint is not known. We addressed this issue by measuring, in the anesthetized rat, the diameters of the common carotid and femoral arteries with an echo-Doppler device (NIUS 01). Blood pressure was measured by a catheter inserted contralaterally and symmetrically to the vessel where the diameter was measured. Arterial distensibility over the systolic-diastolic pressure range was calculated according to the Langewouters formula. Data were collected in 10 intact (vehicle pretreatment) and 9 sympathectomized (6-hydroxydopamine pretreatment) 3-month-old Wistar-Kyoto rats. Compared with the intact animals, sympathectomized rats showed a marked increase in arterial distensibility over the entire systolic-diastolic pressure range. When quantified by the area under the distensibility-pressure curve, the increase was 59% and 62% for the common carotid and femoral arteries, respectively (P<.01 for both). In the femoral but not in the common carotid artery, sympathectomy was accompanied also by an increase in arterial diameter (+18%, P<.05 versus intact). Therefore, in the anesthetized normotensive rat, sympathetic activity exerts a tonic restraint on large-artery distensibility. This restraint is pronounced in elastic vessels and even more pronounced in muscle-type vessels.     

Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS

The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in 11 men who experienced different rates of CD4+ cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently, slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4+ cell count decline. Except for the fastest progressors to AIDS, highly diverse quasispecies developed in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients. Individuals who maintained high CD4+ cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients. The limited number of variants that grew out in short-term PBMC cocultures were rare in the uncultured proviral quasispecies of healthy, long-term infected individuals but more common in vivo in patients with low CD4+ cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies.     

Effect of chemotherapy on the larval mass and the long-term course of alveolar echinococcosis. Swiss Echinococcosis Study Group

The efficacy of long-term chemotherapy in nonresectable alveolar echinococcosis is debated, particularly because of the difficulty in defining therapeutic success. In this study the effect of chemotherapy on the parasitic mass was evaluated in a series of 37 patients. The patients had larval lesions documented by serial computed tomography studies at least 1.5 yr after chemotherapy (mean = 6.4 yr, range = 1.5 to 10.7 yr). The therapeutic regimen consisted of mebendazole (n = 34) or albendazole (n = 3) as previously described. The maximal areas of the parasitic lesions were assessed morphometrically by means of digital image analysis, utilizing the point-integration method, before and after chemotherapy. Marked regression of larval tissue occurred in 18 patients (group A; 48.6%), stationary lesions were noted in 13 patients (group C; 35.1%) and progression was found in 6 patients (group B; 16.2%). The three groups did not differ significantly with regard to age, plasma drug levels, duration of chemotherapy or initial size and composition of lesions (e.g., cystic cavities, degree of calcification). Despite morphologically successful chemotherapy in moist patients (e.g., 84%; groups A and C), late cholestatic complications after 1.5 to 11 yr of chemotherapy occurred in 10 patients (group A, n = 7; group C, n = 3; 4 of them died) and esophageal variceal bleeding occurred in 3 patients (relieved by sclerotherapy). These late complications were probably mainly due to posttherapy fibrosis of hilar structures. In conclusion, our data support the efficacy of chemotherapy. However, chemotherapy is not curative, and severe late complications were observed in patients with hilar (fibrotic) involvement.     

Food intake is inversely correlated with central nervous system histamine receptor (H1) concentrations in male Sprague-Dawley rats fed normal, low protein, low energy or poor quality protein diets

The reported studies were designed to examine relationships between whole-brain histamine receptors (H1) and food intake in male Sprague-Dawley rats. Three different experiments were conducted. In each experiment, control rats were fed normal protein (25 g casein/100 g food) and normal metabolizable energy (16.21 kJ/100 g food) diets. Feeding low protein diets (1 g casein/100 g food) elevated central H1 receptor concentrations (P < 0.0027) and reduced voluntary food intake (P < 0.007) compared with normal diets. Feeding low energy diets lowered H1 receptor concentrations (P < 0.0089) and increased voluntary food intake (P < 0.0012). Low quality protein diets also affected the central nervous histaminergic system. Whole-brain H1 receptor concentrations were significantly higher for rats fed low quality protein (25 g gelatin/100 g food) compared with rats fed casein (P < 0.0001). Rats fed medium quality protein (25 g wheat gluten/100 g food) or low quality protein ate significantly less food (P < 0.0001). In all experiments, dietary manipulation affected central histamine receptors. Elevated concentrations of H1 receptors were associated with a decrease in food intake whereas lowered concentrations of H1 receptors were associated with an increase in food intake (P < 0.001). The results of these experiments support the hypothesis that central histamine H1 receptor concentrations in male rats are inversely correlated with voluntary food intake and affected by dietary composition.     

Comparison of circumsporozoite proteins from avian and mammalian malarias: biological and phylogenetic implications

The circumsporozoite (CS) protein of malaria parasites (Plasmodium) covers the surface of sporozoites that invade hepatocytes in mammalian hosts and macrophages in avian hosts. CS genes have been characterized from many Plasmodium that infect mammals; two domains of the corresponding proteins, identified initially by their conservation (region I and region II), have been implicated in binding to hepatocytes. The CS gene from the avian parasite Plasmodium gallinaceum was characterized to compare these functional domains to those of mammalian Plasmodium and for the study of Plasmodium evolution. The P. gallinaceum protein has the characteristics of CS proteins, including a secretory signal sequence, central repeat region, regions of charged amino acids, and an anchor sequence. Comparison with CS signal sequences reveals four distinct groupings, with P. gallinaceum most closely related to the human malaria Plasmodium falciparum. The 5-amino acid sequence designated region I, which is identical in all mammalian CS and implicated in hepatocyte invasion, is different in the avian protein. The P. gallinaceum repeat region consists of 9-amino acid repeats with the consensus sequence QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which is associated with targeting the invasion of liver cells, is also conserved in the avian protein. Phylogenetic analysis of the aligned Plasmodium CS sequences yields a tree with a topology similar to the one obtained using sequence data from the small subunit rRNA gene. The phylogeny using the CS gene supports the proposal that the human malaria P. falciparum is significantly more related to avian parasites than to other parasites infecting mammals, although the biology of sporozoite invasion is different between the avian and mammalian species.     

Mechanism of mosaic attenuation of the lungs on computed tomography in induced bronchospasm

The purpose of this study was to investigate whether hypoxic pulmonary vasoconstriction is the major determinant of the computed tomography (CT) pattern of mosaic attenuation in asthmatic patients with induced bronchoconstriction. Thin-section CT was performed at suspended full inspiration immediately and 30 min after methacholine bronchoprovocation in 22 asthmatic subjects, who were randomly assigned to breathe room air (group A, n = 8), oxygen via nasal prongs at 5 l/min (group B, n = 8), and oxygen via face mask at 12 l/min (group C, n = 6). CT changes were quantified in terms of global lung density and density in hypodense and hyperdense areas. Lung parenchymal density increases were greatest in group C and greater in group B than in group A, globally (P = 0.03) and in hypodense regions (P = 0.01). On bivariate analysis, the only change in cross-sectional area was related to change in global density. In hypodense regions, density change was related both to reduction in cross-sectional area (P < 0.0005) and to oxygen administration (P = 0.01). After correction for changes in global lung density, only oxygen was independently related to density increase in hypodense areas (P = 0.02). In induced bronchoconstriction, the CT appearance of mosaic attenuation can be largely ascribed to hypoxic vasoconstriction rather than to changes in lung inflation.     

Effect of bioactive glass granules and polytetrafluoroethylene membrane on repair of cortical bone defect

The effect of bioactive glass (BG) granules and nonresorbable polytetrafluoroethylene (PTFE) membrane on the repair of cortical bone defects was studied. Monocortical holes (diameter 3.0 mm) were drilled in rabbit tibia. Sixteen holes were filled with BG granules (diameter 630–800 m). Twelve holes were left empty and covered with PTFE membrane. No material was used at ten control holes. All experiment areas were covered with periosteum attached to the soft tissue flap. Histomorphometric evaluation of resection specimens showed that new bone and glass particles formed a continuous bridge in the BG group at the upper part of the hole, occupying 73.6% and 61.7% of the defect at 6 and 12 weeks, respectively. If only the amount of bone but not glass particles was included in the measurements the corresponding figures were 31.4% and 41.5%. The bone repair in the PTFE group was 12.1% and 11.3% and in the control group 25.1% and 23.3% at 6 and 12 weeks, respectively. The results indicate that BG granules improve repair of cortical bone defects and PTFE membrane seems to impair bone formation in these defects.     

Diuretics and diabetes mellitus

The term "diuretics" describes a concerning pharmacological action and side effects heterogeneous class of drugs. The special advantage of using diuretics includes reducing edema and expanded plasma volume often associated with hypertension and cardiovascular disease. Diuretics are one of the 5 major classes of antihypertensive agents recommended for the initial drug therapy of hypertension. However, currently treatment of hypertension with diuretics is controversial, because of potentially adverse effects on the cardiovascular risk profile, including deterioration in glucose control especially in patients with impaired glucose tolerance. Additionally there is concern about excess mortality associated with diuretic therapy and diabetes mellitus. The metabolic side effects on glucose metabolism and lipid profile are related to the type of diuretic and its dosage. The adverse effects of thiazides on insulin action, glycemia and lipid profile are dose dependent and can be minimized by using low doses. In contrast, indapamide seems not to alter glucose metabolism and lipid profile. The choice of diuretic depends on concomitant disease. In patients with nephropathy potassium sparing agents should not be used, however furosemid can be used even in high doses. Beside focus on indication of diuretics in patients with diabetes and their metabolic side effects treatment of therapy resistant hypertension in these patients are discussed in this review.