Search PubMed⌕ Search

Biomedical subjects

C Grau

Publications and source records attributed to C Grau.

At least 55 records · Page 3Linked to original sources

Subpressor doses of angiotensin II do not increase albumin excretion in humans.

The objective of our study was to evaluate the effects of subpressor doses of angiotensin II and mild physical stress on renal hemodynamics and urinary albumin excretion (UAE) in a group of young patients with essential hypertension compared to normotensive subjects. Eleven patients (26 +/- 6 years) and ten healthy control persons (25 +/- 2 years) were enrolled in the study. Secondary forms of hypertension had been excluded. Angiotensin II was infused at a dose of 0.3 and 1.0 ng/kg/min and physical stress testing was done with a cycle ergometer (50 W at 10 min for hypertensives, 100 W at 10 min for normotensives). Renal hemodynamics were assessed by clearance techniques (continuous insulin and p-aminohippurate clearance). Mean arterial pressure (MAP) and UAE were significantly higher in the hypertensive group than in normotensive control persons at any time of measurement. There was no significant increase in MAP or UAE under angiotensin II infusion either in the hypertensive group or in the normotensive group. MAP increased significantly under physical stress in the normotensive group only (83 +/- 7 mmHg baseline vs. 108 +/- mmHg during physical stress, p < 0.05). Angiotensin II infusion resulted in a significant change concerning renal hemodynamics in the hypertensive group only. The filtration fraction increased (18 +/- 3% baseline vs. 25 +/- 7% under infusion of 1.0 ng/kg/min angiotensin II, p < 0.05) due to a decline in ERPF and an increase in GFR in the hypertensive group. The amount of UAE correlated with the magnitude of the MAP in both groups. No correlation was found between renal hemodynamic parameters and the UAE. A significant correlation was found between the norepinephrine levels and the UAE in the control group. We could not demonstrate an albuminuric effect of subpressor doses of angiotensin II in normotensive or hypertensive subjects despite its well known effects on renal hemodynamics with an increase of the filtration fraction. These data provide evidence against a predominant role of angiotensin II and renal hemodynamics concerning the elevated urinary albumin excretion in young patients with arterial hypertension.

Adult↗

Ultradian rhythms in gross motor activity of adult humans.

During waking h, the existence of ultradian rhythms in gross motor activity has been described in nonprimates, nonhuman primates and newborn humans, but not in adult humans. Some of the previous studies suggested that the appearance of these rhythms could be favored by conditions of isolation and low environmental demands. To confirm the existence of ultradian rhythmicity in the gross motor activity of adult humans and to describe their characteristics, an actimeter was used to record the mobility of 13 adults who remained alone and isolated for 5 h (15:00-20:00) in a monotonous environment with nothing to do. Least squares rhythmometry analysis showed that the gross motor activity of 12 out of 13 subjects had significant rhythms (p < 0.05) within the ultradian band, with periods of between 0.5 and 2.5 h. There were important individual differences between the dominant periods and the same subject might show more than one significant period. These rhythms were stable and they tended to appear immediately the experiment began. The results suggest that a philogenetically old mechanism that organizes gross motor activity in ultradian rhythms exists in adult humans.

Activity Cycles↗

Reoxygenation in a C3H mouse mammary carcinoma. The importance of chronic rather than acute hypoxia.

The role that chronic and acute hypoxia play in tumour reoxygenation after irradiation was investigated in a C3H mouse mammary carcinoma grown in the feet of female CDF1 mice. Tumours at 200 mm3 in size were locally irradiated with a priming dose of 20 Gy and then at various times after given a range of radiation doses under normal or clamped conditions. Local tumour control was determined 90 days later from which the tumour hypoxic fractions were calculated. Untreated tumours contained 23% hypoxic cells. Immediately after 20 Gy this increased to 52% and by 24 h had fallen to 10%. These reoxygenation experiments were repeated, giving either nicotinamide (1000 mg/kg; i.p. injected 30 min before each irradiation) to remove acute hypoxia, or carbogen breathing (for 5 min before and during irradiation) to decrease chronic hypoxia. With nicotinamide the normal hypoxic fraction was reduced to 7%, but after irradiation it had risen to 46% and by 24 h there was full reoxygenation with a value of 5% being observed. Carbogen breathing also decreased the normal hypoxic fraction to 6%, and immediately after irradiation this was increased to 38%. However, by 24 h it was still elevated at around 23%. These results suggest that chronic rather than acute hypoxia is necessary for reoxygenation in this tumour.

Animals↗

Relationship between tumour oxygenation, bioenergetic status and radiobiological hypoxia in an experimental model.

Tumour oxygenation and bioenergetic status were measured in the same tumour and these results related to radiobiological hypoxia. A C3H mouse mammary carcinoma grown in the feet of CDF1 mice was used. Bioenergetic status was assessed by 31P MRS using a SISCO 7 Tesla magnet, oxygen measurements were done by a polarographic electrode and the hypoxic fraction was determined from direct analysis of the radiation dose-response data. During all examinations restrained, non-anaesthetized mice were allowed to breathe either 100% oxygen, carbogen, normal air, carbon monoxide (CO) at 75, 220, or 660 ppm or had blood flow occluded by clamping. Results showed a significant correlation between the radiobiological hypoxic fraction and % pO2 < or = 5 mmHg under the different treatment conditions, whereas no correlation was found between beta nucleosidetriphosphate/inorganic phosphate (beta-NTP/Pi) ratio and either the hypoxic fraction or the % of pO2 values < or = 5 mmHg under the different treatment conditions. In conclusion, oxygen electrode measurements were sensitive to changes in tumour hypoxia whereas the bioenergetic status alone seemed to be a less precise measure of hypoxia in this tumour model. Furthermore, the present study demonstrated that tumour cells in vivo can actually maintain the bioenergetic status during a period of severe hypoxia.

Animals↗

The in vivo interaction between vincristine and radiation in a C3H mammary carcinoma and the feet of CDF1 mice.

PURPOSE: Evaluation of the interaction between vincristine (VCR) and X rays in a murine tumor and its surrounding skin. METHODS AND MATERIALS: End points were local tumor control and moist desquamation using the C3H mammary carcinoma and the mouse foot skin in vivo. Cell cycle effects of VCR was studied by dual parameter flowcytometry. Vincristine was administered as a single IP injection at various time intervals from 4 days before to 4 days after irradiation. RESULTS: Flowcytometric studies of cell cycle distribution showed that VCR caused a temporary blockage of cells in the mitotic phase; the proportion of cells in G2M increased three-fold at intervals up to 48 h after VCR treatment. The radiation enhancement peaked when VCR was administered 24 h before X rays in tumors, and when given 15 min before X rays in skin. A significant therapeutic gain was observed at the 24 h preirradiation of postirradiation intervals--the therapeutic gain factors being 1.19 and 1.24, respectively (p < 0.005). Analysis of the tumor data suggested an additive cytotoxic effect rather than VCR radiosensitization. In contrast to what was expected from the single dose data, a significant loss of therapeutic effect was found for the addition of VCR administered at the first day of a fractionated irradiation regime with five fractions in 5 days (p < 0.025). CONCLUSION: The tumor control studies showed a lack of correlation between the VCR-induced accumulation of cells in G2M cell cycle phase and enhancement of tumor radiation response. Preirradiation VCR caused radiosensitization both in tumors and skin, whereas postirradiation VCR mostly resulted in responses equal to radiation only.

Animals↗

Relationship between radiobiological hypoxia in tumors and electrode measurements of tumor oxygenation.

PURPOSE: To determine whether electrode measurements of tumor oxygenation, made in a variety of murine tumor models, correlate with estimates of radiobiological hypoxia in the same tumor systems. METHODS AND MATERIALS: The tumor models used were a C3H mammary carcinoma grown in the feet of CDF1 mice; the SCCVII, KHT and RIF-1 tumors grown in the feet or flanks of C3H/Km mice; and the CaNT and SaF tumors grown on the backs of CBA mice. All treatments were performed when tumors were about 200 mm3 in size. Radiobiological hypoxic fractions were determined using either a paired survival curve assay, with survival measured 0-24 h after irradiation, or using a clamped tumor control assay, with percent local tumor control estimated 90 days after treatment. Measurements of tumor oxygen partial pressure (pO2) distributions were performed using Eppendorf oxygen electrodes. RESULTS: The hypoxic fractions determined from the radiation response data were about 1% in RIF-1 and SCCVII, 12% in C3H and KHT, 28% in CaNT and up to 38% in SaF tumors. When this data was compared with the tumor oxygenation measurements it was found that as hypoxic fraction increased the mean, median, and the percentage of pO2 values < or = 5 mmHg showed a trend towards poorer oxygenation status. However, none of these pO2 changes were significantly correlated with hypoxia. Moreover, the pO2 values < or = 2.5 mmHg indicated an improvement in oxygen status with increasing hypoxic fraction. CONCLUSION: Electrode measurements of tumor oxygenation alone may, therefore, not be a good indicator of tumor hypoxia across different tumor cell lines.

Animals↗

Effect of carbon monoxide breathing on hypoxia and radiation response in the SCCVII tumor in vivo.

PURPOSE: To study the influence of a clinically relevant concentration of carbon monoxide (CO) on tumor oxygenation and response to irradiation. METHODS AND MATERIALS: The murine tumor model was the SCCVII squamous cell carcinoma transplanted to the feet of C3H/Km mice. RESULTS: Sixty minutes of breathing CO at 200 ppm resulted in a carboxyhemoglobin level of 15%. This resulted in a reduction in p50 (the oxygen partial pressure at which hemoglobin is 50% saturated) to 78% of the control value, and a decrease in tumor blood perfusion to 73% of the control value. The combined effect of a decrease in effective hemoglobin and blood perfusion resulted in a reduction in tumor oxygen supply to 62% of the control value. In agreement with this, intratumoral pO2 measurements showed a significant increase in tumor hypoxia, such that the percentage of measurements with low pO2 (< or = 5 mmHg) increased from 33% to 62%. The fraction of clonogenic hypoxic cells, measured radiobiologically by paired cell survival curves, similarly increased from 0.2% to 3.8%. Radiation sensitivity, evaluated from in vivo-in vitro excision assay, was significantly decreased by CO breathing with both single dose and fractionated irradiation. The observed enhancement ratios for radiation given in 1, 4, 8, and 12 fractions were 0.71, 0.77, 0.83, and 0.71, respectively. CONCLUSION: The present SCCVII tumor data confirm the general experimental observation that CO breathing significantly increases tumor hypoxia and reduces the effectiveness of ionizing irradiation.

Animals↗

Reversibility of brain-stem evoked potential abnormalities in abstinent chronic alcoholics: one year follow-up.

Brain-stem auditory evoked potentials (BAEPs) were studied in 34 chronic alcoholics who had been abstinent for 1 year, and in age- and sex-matched control subjects. The patients were examined 3 times, at 1 month, 5 months and 1 year after the start of the abstinence treatment. At 1 month of abstinence the alcoholics showed differences with respect to controls in the peak V latency (P < 0.01), and in the III-V (P < 0.01) and I-V (P < 0.01) intervals. After 1 year of abstinence a significant improvement in the V (P < 0.01), III-V (P < 0.01) and I-V (P < 0.01) parameters was recorded. The most notable development was in the 5-12 month period, with shortening in V latency (P < 0.01) and in the I-V interval (P < 0.01); in the first 5 months there was only shortening in the III-V interval (P < 0.01). This improvement was also indicated by a decrease in the number of patients with BAEP parameter abnormalities. The recovery of the functions impaired by chronic alcohol consumption after 1 year of abstinence was incomplete, although the tendency was towards normalization.

Acoustic Stimulation↗

The relationship between carbon monoxide breathing, tumour oxygenation and local tumour control in the C3H mammary carcinoma in vivo.

The effect of acute carbon monoxide (CO) breathing on blood oxygenation and tumour hypoxia was related to the radiation response of the C3H/Tif mammary carcinoma. Blood gas analysis showed that CO breathing caused a time- and dose-dependent formation of carboxyhaemoglobin (HbCO), a significant left shift of the oxygen dissociation curve and a reduction in tumour blood perfusion. These factors all contributed to a marked drop in tumour oxygen supply. In agreement with this, tumour hypoxia was found to be significantly increased: Microelectrode PO2 measurements showed a clear relationship between CO concentration and the proportion of low PO2 measurements (< or = 5 mmHg). The fraction of clonogenic hypoxic cells increased from 8% in air-breathing animals to 13%, 18% and 54% with 75,220 and 660 p.p.m. CO respectively. The tumour hypoxia resulted in significant radiation modification. The local tumour control after single-dose and fractionated irradiation gave TCD50 enhancement ratios (relative to air-breathing controls) of 0.90, 0.85 and 0.89 for single dose and five or ten fractions given in 5 days (P < 0.005 for all values). For 15 fractions in 5 days with 6- 6- and 12 h intervals, the TCD50 was similar in CO- and air-breathing mice, presumably as a consequence of insufficient reoxygenation during the short inter-fraction intervals. It is concluded that elevated HbCO levels to increased tumour hypoxia and that the induced hypoxia has a significant impact on the local tumour control also after fractionated irradiation.

Animals↗

Ultradian rhythms in selective auditory attention performance.

In order to study the existence of ultradian rhythms in human performance, reaction times and omissions of responses to signal stimuli were registered from 17 subjects performing a selective auditory attention task, at 15-minute intervals from 9:00 am to 3:00 pm. The task consisted of selectively focusing attention, first to the left and then to the right ear, and pressing a button every time a signal stimulus was detected. Rhythmometric analysis showed the existence of significant (p < .05) ultradian rhythms both in the temporal course of the reaction time and in the number of omissions of responses to signal stimuli. Results are discussed in terms of the level of difficulty of the task and the processing resources involved.

Acoustic Stimulation↗

[Damage to the spinal medulla caused by radiation].

The current clinical and biological knowledge about radiation myelopathy is reviewed. Transient myelopathy with Lhermitte's sign develops within months after irradiation. Symptoms generally disappear within months without treatment. Chronic progressive radiation myelopathy develops with a latency of several months to years after spinal cord irradiation. The symptoms are paraesthesia, paresis or paralysis, leading to severe physical disability and eventually death due to secondary infections. The long term survival after myelopathy is 30% for cervical myelopathy and 70% for thoracic myelopathy. There is no effective treatment. Analysis of clinical reports shows that the risk of developing chronic myelopathy is less than 2% after 55 Gy, given in 2 Gy daily fractions. Other important radiobiological risk factors (dose per fraction, interfraction interval and volume) are discussed.

Chronic Disease↗

Diurnal type and hemispheric asymmetry.

Monk and Leng (1986) postulated that Morning-types (M-types) rely more than Evening-types (E-types) on subvocalization strategies, indirectly suggesting a difference in their habitual mode of hemispheric engagement. To evaluate this hypothesis, 48 right-handed women, 24 M-types and 24 age-matched E-types, performed verbal and spatial hemifield tachistoscopic tasks and recorded oral temperature at four separate times of day. Oral temperature curves were larger in amplitude and phase delayed for E-types. Reaction time curves were slower for E-types, without M-E phase differences. Error rate curves showed significant time-of-day effects at left-visual-field verbal tasks for M-types and at right-visual-field spatial tasks for E-types, indicating a selective trend in relying on left hemispheric mode for M-types and on right hemispheric mode for E-types. Implications for circadian oscillatory control are discussed.

Adolescent↗

Diurnal oscillations in hemispheric performance.

Folkard (1979, 1990) suggested that diurnal changes in performance may reflect a morning-evening decrease in the degree of left-hemisphere dominance. Forty-eight right-handed women performed verbal and spatial hemifield tachistoscopic tasks at four separate times of day. Supporting the above hypotheses, changes in accuracy over the day showed a left-hemisphere advantage at 12:00 and a right-hemisphere advantage at 19:45, whereas changes in speed were symmetrical both in verbal and spatial tasks. These changes occurred only when hemispheres received stimuli in the processing of which they were not specialized, that is, when verbal stimuli appeared at the left visual field and spatial stimuli at the right visual field. Evidence suggesting a separate oscillatory control of the circadian rhythms of left and right-hemisphere activity is discussed.

Adolescent↗

Auditory brain stem responses in patients after radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The study evaluated the incidence and severity of brain stem myelopathy occurring after radiation exposure in a cohort of patients who received external radiation exposure for nasopharyngeal carcinoma (NPC). METHODS: Brain stem function was investigated by auditory brain stem responses (ABR). RESULTS: Four of 21 patients who could be examined had aberrations in ABR. Three patients showed highly abnormal ABR, with no distinctive patterns or peaks. Two of these patients also showed clinical symptoms of brain stem dysfunction, including multiple palsies in cranial and peripheral nerves, whereas the third patient had no clinical signs of brain stem disorders. The fourth patient had minor conduction delays in ABR. The remaining group of 17 patients who could be examined had ABR latency and transmission times similar to those of the control group. None of these patients had neurologic symptoms. Dose-response analysis showed that patients who received radiation doses of 59 Gy or less to the brain stem had normal ABR, whereas four of six patients who received a dose of 68 Gy had manifest or subclinical brain stem dysfunction. CONCLUSIONS: The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure.

Adult↗

Effect of etoposide, carmustine, vincristine, 5-fluorouracil, or methotrexate on radiobiologically oxic and hypoxic cells in a C3H mouse mammary carcinoma in situ.

The effect of etoposide (VP16), carmustine (BCNU), vincristine (VCR), methotrexate (MTX), and 5-fluorouracil (5-FU) on the oxic and hypoxic cells in a C3H mammary carcinoma in CDF1 mice was investigated using an in situ local-tumor-control (TCD50) assay. The surviving fraction (SF) was calculated from the size of the radiation dose needed to inactivate the surviving tumor cells in drug-treated tumors relative to untreated controls. Preferential drug cytotoxicity towards oxic and hypoxic cells was evaluated from the difference in the response to irradiation under ambient and clamped conditions, respectively. Three drugs caused a significant (P less than 0.05) reduction in the survival of hypoxic cells, the SFs being 0.31 (VP-16), 0.13 (BCNU) and 0.16 (VCR). VCR was also toxic towards oxic cells (SF, 0.17), whereas VP16 and BCNU had no significant effect on these cells (SF, 0.5 and 0.76, respectively). Two drugs produced significant killing of cells in the oxic compartment: 5-FU (SF, 0.10) and MTX (SF, 0.22); these two drugs had no effect on hypoxic cells (SF, 0.78 and 1.11, respectively).

Animals↗

Effect of carboxyhemoglobin on tumor oxygen unloading capacity in patients with squamous cell carcinoma of the head and neck.

Hemoglobin and blood gas parameters, with special attention to the influence of carboxyhemoglobin, were studied in 115 head and neck cancer patients undergoing radiotherapy. In 712 weekly blood samples, the values of total hemoglobin, carboxyhemoglobin (CO-Hb), and p50 were measured and the total oxygen content in the arterial and tumor venous blood was estimated. The difference between these values express the tumor oxygen unloading capacity (t-OUC). CO-Hb ranged from 0-12% and showed a significant inverse relationship with t-OUC. This was caused by a reduced amount of effective hemoglobin combined with a left shift of the oxyhemoglobin dissociation curve (reduced p50). Overall, the tumor oxygen utilization decreased from 70% to 52% as a function of an increase in CO-Hb from 0 to 12%.

Adult↗