Mechanical energy absorption in human hand-arm exposed to sinusoidal vibration

Summary A possible basis for risk assessment of human exposure to vibration when using hand-held tools may be to determine the amount of mechanical energy that is absorbed by the hand-arm system. The aim of this investigation was to study the absorption of mechanical energy in the human hand-arm system during exposure to sinusoidal vibration within the frequency range of 20 to 1500 Hz. A handle, specially designed for this type of experiments, was used during the measurements. The influence of various experimental conditions, such as three different hand-arm postures, grip force (25–75 N) and vibration levels (27–53 mm/s_rms), were studied on eight subjects. The outcome clearly shows that the energy absorption properties of the human hand-arm system are more or less dependent on all of the experimental conditions studied, but mainly to the frequency of the vibration stimuli. Furthermore, the results indicate a non-linear relationship between the energy absorbed and all other variables studies.     

Lactic acid concentration and acid-base balance in cerebrospinal fluid: observations of diagnostic importance in non-Hodgkin lymphoma

Measurements of lactic acid concentration and gas analysis were performed in lumbar cerebrospinal fluid from 36 patients without malignant central nervous system involvement and four patients with meningeal dissemination of non-Hodgkin lymphoma. The upper lactic acid concentration in controls of 2.48 mmol/l was exceeded in all four patients, also in cases with low blast counts and normal protein and glucose content. The pH, pCO2, pO2 and standard bicarbonate concentration in spinal fluid of patients with meningeal dissemination in non-Hodgkin lymphoma did not show significant differences compared with other patients and controls. Determination of the lactic acid concentration in cerebrospinal fluid add information, relevant to the diagnosis of meningeal involvement in non-Hodgkin lymphoma.     

Biodistribution of radioactive epidermal growth factor in normal and tumor bearing mice

The biodistribution of iodinated epidermal growth factor in normal and tumor bearing mice was analyzed. The uptake of epidermal growth factor was high in the liver, skin and submaxillary gland, which all have detected receptors for the growth factor. Organs, such as lung, heart, spleen, intestine, bone and central nervous system, which lack the receptor, did not retain the growth factor. In tumor bearing mice, the growth factor accumulated in receptor positive tumors, but to a lesser extent than in the liver. This finding will probably prevent the use of epidermal growth factor as a carrier for radionuclides for a therapeutic purpose.     

Timing of in-vitro fertilization of cumulus-free and cumulus-enclosed human oocytes

In humans, in contrast to other species, sperm capacitationrequires a very short time, as in-vitro fertilization has beenobtained after only 45 mm of contact between oocytes and spermatozoacapacitated for 1 h. No fertilization occurred, whatever theduration of sperm capacit.ation, when gamete mixing did notexceed 30 mim. On the contrary, 85% of cumulus-free mature oocytesexposed to sperm for 1–4 h were fertilized. The presenceof the pre-ovulatory, fully-expanded or compact cumulus massdid not represent a physical barrier to sperm progression, aswe observed no delay in fertilization when oocytes were enclosedin the cumulus. The use of a short insemination protocol (1–4h instead of 17–20 h) did not reduce the fertilizationrate of denuded or cumulus-enclosed oocytes and had no significanteffect on the morphological appearance of the embryos or theircleavage rates.     

Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies

Experimental Autoimmune Encephalomyelitis (EAE) can be induced in mice of the C57BL/6 strain by subcutaneous immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide p35-55 in CFA, administered twice at an interval of one week and supplemented with Bordetella pertussis toxin given IV. Here, we studied the effect on the induction of EAE of depleting antibodies to CD4, CD8, or CD25 administered before either the first or the second dose of MOG p35-55. We found that anti-CD4 abolished EAE when given before the first immunization; anti-CD4 did not affect the disease when it was given before the second immunization. Anti-CD8 enhanced EAE induction when given before either of the two immunizations. Anti-CD25 enhanced EAE to the same degree as anti-CD8 when given before the first immunization, but anti-CD25 was even more effective in enhancing EAE when given before the second immunization. The anti-CD25 treatment led to significantly enhanced IFNgamma production by T cells responding to MOG p35-55 and persisting anti-MOG antibodies detectable 56 days after the first immunization. Administration of anti-CD8 or anti-CD25 abolished the need for pertussis toxin to induce EAE. These findings are compatible with the idea that CD4 T cells are required for the initial induction of EAE and that the disease is down-regulated by T cells expressing CD8 or CD25. These regulatory T cells exist prior to MOG immunization, but the CD25+ regulators appear to be further amplified by immunization.     

Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in advanced brain tumor patients: preliminary study

High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.     

Serologic detection of infection with cagA+ Helicobacter pylori strains.

Approximately 60% of Helicobacter pylori isolates possess the cagA gene and express its 120- to 140-kDa product (CagA). In this study, the cagA gene was detected in H. pylori isolates from 26 (81.3%) of 32 patients with duodenal ulcers (DU), 17 (68.0%) of 25 patients with gastric ulcers, and 23 (59.0%) of 39 patients with nonulcer dyspepsia (NUD). By Western blotting (immunoblotting) with antiserum to CagA, in vitro CagA expression was demonstrated for 95.5% of cagA+ strains compared with 0% of strains lacking cagA. Sera from patients infected with cagA+ strains (n = 66) reacted with recombinant CagA in an enzyme-linked immunosorbent assay to a significantly greater extent than either sera from patients infected with strains lacking cagA (n = 30) or sera from uninfected persons (n = 25) (P < 0.001). A strain lacking cagA was isolated from eight patients who had serum immunoglobulin G antibodies to CagA, which suggests that these patients were infected with multiple strains. Serum immunoglobulin G antibodies to CagA were present in 87.5, 76.0, and 56.4% of patients with DU, gastric ulcers, and NUD, respectively (odds ratio, 5.41; 95% confidence interval, 1.44 to 24.72; P = 0.004 [DU versus NUD]). These data demonstrate an association between infection with cagA+ H. pylori and the presence of duodenal ulceration and indicate that serologic testing is a sensitive method for detecting infection with cagA+ strains.     

Effects of environmental factors on the number of emergency admissions to the Hospital Complex Juan Canalejo in La Coruña: creation of a prediction model

BACKGROUND: This study is aimed at establishing the possible associations between the number of admissions through the emergency room at the "Juan Canalejol" Hospital in Corunna in 1994-1994 due to organic, circulatory and respiratory reasons and the weather variables introduced as being exogenous for the purpose of preparing a prediction model. METHODS: The Box-Jenkins methodology is used for obtaining univariate ARIMA models of the time-based series taken into consideration. Cross-Correlation Functions (CCF's) are established among the series of residuals which afford the possibility of establishing weights and lags among the variables for a subsequent modeling by means of multivariate ARIMA models which include environmental variables. RESULTS: The emergency admissions for organic reasons significantly increase 0-2 days following a rise in temperature. The admissions due to respiratory ailments are associated with drops in temperature with 10-14 lags, whilst the admissions for circulatory reasons increase significantly due to long-lasting spells of hot weather (10 lags). For people over age 65, significant increases in emergency admissions for circulatory reasons are also recorded with cold snaps. The multivariate ARIMA models that take into account the effect of environmental variables provided the best adjustment for all of the admissions variables. CONCLUSIONS: The number of emergency room admissions at the "Juan Canalejo" Medical Center Complex in Corunna due to organic, respiratory and circulatory causes shows a seasonal behavior pattern. The admissions for respiratory reasons are associated with a drop in temperature, whilst the admissions for circulatory reasons are affected fundamentally by hot weather, although also by cold weather as regards people over age 65. The multivariate ARIMA models including climate-related variables provide a system for predicting admissions in terms of said variables that can be useful from the standpoint of hospital management.     

Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.