Can chromosomal instability initiate tumorigenesis?

Cancers result from the accumulation of inherited and somatic mutations in oncogenes and tumor suppressor genes. These genes encode proteins that function in growth regulatory and differentiation pathways. Mutations in those genes increase the net reproductive rate of cells. Chromosomal instability (CIN) is a feature of most human cancers. Mutations in CIN genes increase the rate at which whole chromosomes or large parts of chromosomes are lost or gained during cell division. CIN causes an imbalance in chromosome number (aneuploidy) and an enhanced rate of loss of heterozygosity, which is an important mechanism of inactivating tumor suppressor genes. A crucial question of cancer biology is whether CIN is an early event and thus a driving force of tumorigenesis. Here we discuss mathematical models of situations where inactivation of one or two tumor suppressor genes is required for tumorigenesis. If two tumor suppressor genes have to be inactivated in rate-limiting steps, then CIN is likely to emerge before the inactivation of the first tumor suppressor gene.     

Coprocessing of powdered cellulose and magnesium carbonate: direct tableting versus tableting after roll compaction/dry granulation

Mixtures of magnesium carbonate (MC) with three types of powdered cellulose (M80, P290, A300) were tableted directly or after roll compaction/dry granulation. The fraction of powdered cellulose in the mixture was varied from 0% to 25% (w/w). The properties of the granules, blends, and their corresponding tablets were analyzed. Granules with a low amount of A300 showed the best flow properties, whereas the fibrous shape of the binding agents M80 and P290 impaired the free flow. Heckel plots showed clearly the different behavior of powdered cellulose in blends and granules during the tableting process. The Heckel-Plots for pure MC powder and granulated MC (MCgr) were similar. Increasing the fraction of powdered cellulose resulted in a fan-shaped set of curves, which is a reflection of an increased densification. Physical mixtures of all three powdered celluloses and granulated mixtures of M80 resulted in a higher densification compared with pure MC. In contrast, the granulated mixtures of P290 and A300 resulted in a diminished densification during tableting, which means that the coprocessed mixtures behaved differently during tableting compared with the physical mixtures. The curves were lower than those of pure MC and MCgr most pronounced at a fraction of 5% powdered cellulose. The tablet pore structure was evaluated by mercury porosimetry. The addition of P290 and A300 to the dry granules resulted in tablets with a higher fraction of smaller pores. Comparably high values for tablet tensile strength and low friability resulted from this special tablet structure. Roll compacted/dry granulated MC, coprocessed with 5% of P290 or A300, seems to be a promising excipient for direct compression. This coprocessed product combines good flow and tablet properties, and is superior to pure MC or a physical mixture of MC and PC.     

Selected disorders of connective tissue: pseudoxanthoma elasticum, cutis laxa, and lipoid proteinosis

There has been progress made in the understanding of 3 Mendelian disorders: pseudoxanthoma elasticum, cutis laxa, and lipoid proteinosis cutis and mucosae. While they are primary connective tissue diseases, their names imply a connection to the skin, and in fact, it is often the dermatologist who makes the diagnosis. It seems rational that defects in various extracellular matrix proteins cause lipoid proteinosis or subtypes of cutis laxa, yet the discovery of a liver- and kidney-based transmembrane transporter as the culprit of pseudoxanthoma elasticum was rather surprising and may shed new light on elastic tissue homeostasis.     

Evaluation of a 16-MDCT scanner in an emergency department: initial clinical experience and workflow analysis

OBJECTIVE: MDCT is especially suited for emergency purposes because it allows rapid high-resolution scans of large areas, fast high-quality reformatting in every orientation, and 3D illustration of the data set. In a prospective study, we evaluated the reliability and workflow of a dedicated emergency department 16-MDCT scanner in the management of patients presenting to the emergency department. SUBJECTS AND METHODS: The use of a 16-MDCT scanner for 503 patients in the emergency department of a university clinic was evaluated. For reasons of workflow analysis, seven precise time intervals were recorded during the emergency examinations. A new setting for repositioning multiple-trauma patients after imaging of the head and neck from the head-first position to the feet-first position was introduced. RESULTS: Six (1.2%) of the 503 patients were excluded because of technical malfunction or patient noncompliance. Image quality in the remaining 497 cases, including CT angiography and CT of multiple-trauma patients, was outstanding. Positioning of the patients took from 3 to 13 min depending on the body region examined, representing 33-67% of the mean room time, which ranged from 8 to 21 min. In multiple-trauma patients, the initial positioning took a mean of 6 min and repositioning took 8 min, representing 19% and 26% of total room time, respectively. CONCLUSION: The use of a dedicated 16-MDCT scanner in the emergency department resulted in short examination times even for examinations of multiple body regions under emergency conditions. The introduced setting-repositioning of multiple-trauma patients-allowed high image quality to be maintained. The trade-off in multiple-trauma patients was prolonged room time because of patient repositioning.     

Histomorphologic examination of skeletal muscle preparations does not differentiate between malignant hyperthermia-susceptible and -normal patients

BACKGROUND: It has been suggested that malignant hyperthermia (MH) can be diagnosed by specific myopathologic alterations. The purpose of this study was to investigate whether there are characteristic myopathologic changes in skeletal muscles of MH-susceptible (MHS) compared with MH-normal (MHN) patients. METHODS: Four hundred forty patients with clinical suspicion of MH were classified as MHN, MH equivocal (MHE), or MHS by the in vitro contracture test with halothane and caffeine. In addition, a small muscle sample excised from each patient was analyzed by histologic, histochemical, immunohistochemical, and computer-aided morphometric methods. RESULTS: MHN was diagnosed in 243 patients, MHE was diagnosed in 65, and MHS was diagnosed in 132. No myopathologic abnormalities were found in 53.5% of the MHN, 53.9% of the MHE, and 56.1% of the MHS patients. Thirty-five percent of all patients showed one, 9.8% showed two, and only 0.9% showed three different pathologic findings within skeletal muscle preparations. The frequency of pathologic findings did not differ between the MHN and the MHS patients; only fiber type I predominance was observed more often in MHN. MHE patients could not be assigned to a diagnostic group by detection of myopathologic alterations. In six clinically unaffected patients, a former unrecognized myopathy, such as central core disease, was diagnosed. This disease is characterized by a specific alteration (cores). CONCLUSIONS: Histologic differences between MHS and MHN statuses could not be demonstrated in this study. Histopathologic examinations can neither improve the diagnosis of MH nor contribute to a better definition of the MH status. However, histopathologic examinations might be useful to detect formerly unrecognized specific myopathies.     

Korean hand acupressure for motion sickness in prehospital trauma care: a prospective, randomized, double-blinded trial in a geriatric population

Patients with trauma or medical illnesses transported to the hospital by ambulance have a frequent incidence of motion sickness. Because the administration of drugs in the ambulance is prohibited by law in Austria, the noninvasive Korean hand acupressure point at K-K9 may be an alternative against nausea and vomiting. We enrolled 100 geriatric patients with minor trauma, randomizing them into a K-K9 group and a sham acupressure group. We recorded visual analog scores (VAS) for nausea and for the patient's overall satisfaction with the treatment, hemodynamic variables, and peripheral vasoconstriction. In the K-K9 group, a significant (P < 0.01) increase in nausea was recorded in all cases: from VAS of 0 mm to 25 +/- 6 mm. A similarly significant (P < 0.01) increase was registered in the sham group: from VAS of 0 mm to 83 +/- 8 mm. However, at the time of arrival in the hospital, nausea scores were significantly different between the K-K9 group and the sham group (P < 0.01). Although all patients had been vasoconstricted at the emergency site before treatment, there was a significant difference (P < 0.01) between groups with regard to the number of vasoconstricted patients at the hospital (4 and 46 constricted and dilated, respectively, in the K-K9 group versus 48 and 2 constricted and dilated, respectively, in the sham group). On arrival in the hospital, a significant difference (P < 0.01) in heart rate was noted between the K-K9 group and the sham group (65 +/- 6 bpm versus 98 +/- 8 bpm). The patients' overall satisfaction with the provided care was significantly higher (P < 0.01) in the K-K9 group (19 +/- 9 mm VAS) than in the sham group (48 +/- 12 mm VAS). Neither group experienced a significant change in blood pressure. K-K9 stimulation was an effective and simple treatment for nausea during emergency care and significantly improved patient satisfaction. IMPLICATIONS: Korean hand acupressure at the K-K9 point was effective in reducing nausea and subjective symptoms of motion sickness in emergency trauma transport of patients at high risk of motion sickness.     

Interleukin 4 increases the antibody response against Rubisco in mice

The influence of interleukin 4 (IL-4) on antibody titer in serum and spleen culture supernatant in mice immunized with spinach (Spinacia oleracea L.) Rubisco was investigated. Therefore, we boosted one mouse additionally to the antigen with recombinant mouse IL-4. We found that the Rubisco-specific antibody titer in serum as well as in spleen cell culture supernatant was significantly enhanced in the IL-4 mouse. Most of the antibodies were of the IgG1 subclass. After hybridoma generation, Rubisco-specific antibodies were found in more than 95% of the wells tested compared to about 12% of the control mouse.     

Pharmacy cost evaluation of risperidone, olanzapine, and quetiapine for the treatment of schizophrenia in acute care inpatient settings

OBJECTIVE: This study examines total pharmacy cost and usage patterns of schizophrenic patients in acute mental health inpatient settings for three atypical antipsychotics -- risperidone, olanzapine, and quetiapine. Despite the readily available unit cost information for drugs, actual pharmacy costs may deviate significantly from 'labeled costs'. Recent research findings indicate the need for more robust evaluation of such pharmacy costs. RESEARCH DESIGN AND METHODS: This study used data from non-randomized inpatient retrospective charts from three acute care inpatient mental health facilities. The final pooled sample included 327 patients, of which 120 received risperidone, 153 received olanzapine, and 54 received quetiapine. Medication cost was defined as the average wholesale price (AWP) as listed in the 2001 'Red Book'. Propensity scoring methodology and multinomial regression were employed to reduce treatment selection bias. RESULTS: The observed mean daily antipsychotic drug doses were 4.45 mg (SD 2.44) for risperidone, 14.04 mg (SD 5.55) for olanzapine, and 350.33 mg (SD 228.24) for quetiapine. The corresponding mean daily drug costs were $7.66(SD $4.20) for risperidone, $8.11 (SD $5.29) for quetiapine and, $12.10 (SD $4.79) for olanzepine. Numbers adjusted for treatment selection bias show that the average daily total pharmacy cost of risperidone was $4.35 lower than olanzapine (p < 0.001) and $1.41 lower than quetiapine (p = 0.38). The adjusted average daily pharmacy cost of olanzapine was $4.02 higher than quetiapine (p < 0.001). After statistical adjustment there were no significant differences between study drugs in terms of length of stay or patient functioning. CONCLUSION: This study provides the first US comparison of medication utilization patterns and pharmacy costs for olanzapine, risperidone, and quetiapine administered in acute mental health care inpatient settings. While this study did not estimate the full economic value of the three antipsychotics in these inpatient settings, it demonstrated that the mean daily costs for risperidone were lower than the mean daily costs for olanzapine (p < 0.001) and quetiapine although the later difference was not statistically significant (p = 0.38).