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Biomedical subjects

N Rossing

Publications and source records attributed to N Rossing.

At least 37 records · Page 2Linked to original sources

Bronchoscintigraphic visualization of the acute effect of tobacco exposure and terbutaline on mucociliary clearance in smokers.

The aim of this study was to examine the acute effect of tobacco smoke exposure and inhaled terbutaline on mucociliary clearance in 9 healthy smokers. It was based on a recently described method for scintigraphic visualization of the bronchi (bronchoscintigraphy). After an initial bronchoscintigram had been made by having the subjects inhale aerosolized 99mTc-albumin, they inhaled either terbutaline or placebo from a metered-dose inhaler. Subsequently, data acquisition for production of bronchoscintigrams was repeated at 10 min intervals for 120 min, and the mucociliary clearance was estimated from the movement of radioactivity in the series of bronchoscintigrams thus obtained. On two study days the subjects remained tobacco abstinent, while on two occasions they chain-smoked during the examination. Acute tobacco exposure resulted in an increased clearance rate in the lobar bronchi in 8 of the 9 smokers (p less than 0.03), while in the main bronchi and the trachea the effect was inconsistent. In all subjects terbutaline systematically increased the clearance rate in all visible bronchial structures compared to placebo (p less than 0.04). The combination of smoking and terbutaline caused a faster clearance rate in the lobar bronchi in most subjects than tobacco smoke or terbutaline alone. It is concluded that both acute tobacco exposure and terbutaline increase mucociliary clearance in healthy smokers.

Adult↗

Effects of cisplatin on different measures of glomerular function in the human kidney with special emphasis on high-dose.

To investigate the effect of high-dose cisplatin (40 mg/m2 daily for 5 days), 51Cr-EDTA clearance was used as a measure of glomerular filtration rate (GFR). 51Cr-EDTA clearance decreased significantly from 109 +/- 3 ml/min * 1.73 m2 to 68 +/- 3 ml/min * 1.73 m2 after three cycles of cisplatin and remained at this decreased level during the observation period (24 months). To determine the reliability of creatinine as a measure of GFR, we compared the simultaneous clearance of creatinine to that of 51Cr-EDTA. A good correlation between 51Cr-EDTA clearance and creatinine clearance was observed before and 3 months after termination of treatment, but no correlation was found during treatment. S-creatinine decreased significantly during treatment, probably due to muscle wasting. We conclude that s-creatinine and creatinine clearance are unsuitable measures of glomerular function during high-dose cisplatin treatment. All patients developed proteinuria during treatment. The changes in clearance ratios of beta-2-microglobulin/albumin and IgG/albumin show that the proteinuria observed during cisplatin infusion is predominantly of tubular origin, whereas the proteinuria between the treatment periods is mainly of glomerular origin.

Adult↗

Determination of the mean transit time for the transport of aerosolized 99mTc-DTPA across the pulmonary epithelial membrane. A plasma sample method.

During the last decade it has been customary to estimate pulmonary epithelial permeability (P-P) as the pulmonary clearance of inhaled nebulized 99mTc-DTPA from a time-activity (t-a) curve registered externally by monitoring over the chest. The t-a curve, however, is not defined by the degree of P-P alone but also by factors such as the deposition of the 99mTc-DTPA in the lungs. To avoid these problems a plasma sample method was derived. It describes P-P by the mean transit time (t) for the transport of 99mTc-DTPA across the pulmonary epithelial membrane, t(L). The calculation of t(L) involves two steps. Following the inhalation of Tc-DTPA the plasma t-a curve is defined and used to calculate t for the transport for 99mTc-DTPA across the pulmonary epithelial membrane, through the ECV and until elimination by the kidneys, t(L+ECV). Subsequently, 99mTc-DTPA is injected as a bolus i.v. and the new t-a curve is used to calculate t for the transport of 99mTc-DTPA through ECV to the kidneys, t(ECV). Finally t(L) is calculated as t(L) = -t(L + ECV) t(ECV). We applied the method in nine non-smoking individuals (median age 25.5 years, range 20-28) and compared the results to t as calculated from the initial slope of an externally derived t-a curve. The individual t(L) values were systematically greater than those of the external detection method (P less than 0.05). It is concluded that the initial slope method overestimates total PC1 as measured by the plasma sample method. When choosing between the two methods, special interest should be paid to the inherent problems of the methods.

Adult↗

Imaging of the airways by bronchoscintigraphy for the study of mucociliary clearance.

A method for functional imaging of the large airways (bronchoscintigraphy) has been developed. It is based on the administration of aerosolised albumin labelled with technetium-99m using a special inhalation technique to produce central airway deposition. The method was evaluated as a measure of mucociliary clearance by recording the movement of radioactivity in the airways of 11 healthy, non-smoking subjects on two separate days. A series of bronchoscintigrams was acquired at five minute intervals for two hours after termination of the inhalation. After the first bronchoscintigram 1.25 mg terbutaline or placebo was administered from a metered dose inhaler (five puffs) according to a randomised, double blind, crossover design. The scintigrams were evaluated blind. After terbutaline the segmental bronchi were no longer visible after a median time of 10 minutes, the lobar bronchi after 20 minutes and the main bronchi after 30 minutes. In six cases the trachea was cleared after two hours. After placebo the segmental bronchi disappeared after a median of 15 minutes, but at two hours half the lobar bronchi remained visible. In only two cases was it no longer possible to see the main bronchi or the trachea. It is concluded that bronchoscintigraphy can be used to examine regional mucociliary clearance in healthy subjects and that terbutaline significantly increases the clearance of the deposited radioactive aerosol.

Administration, Inhalation↗

Long-term effects on renal function and blood pressure of treatment with cisplatin, vinblastine, and bleomycin in patients with germ cell cancer.

Long-term effects of cisplatin on renal function were investigated in 34 patients with germ cell cancer observed for a median of 65 months (range, 43 to 97 months). All patients achieved a complete remission after treatment with cisplatin (median dose 583 mg/m2), vinblastine, and bleomycin. None of the patients relapsed during follow-up. During treatment the glomerular filtration rate (GFR) decreased by 18% (P less than .05). During follow-up kidney function recovered in ten patients and partly improved in eight patients. Changes in plasma creatinine did not consistently correspond to alterations in GFR. The mean increase in systolic blood pressure during follow-up did not differ from the increase seen in a group of age-matched healthy men. The mean increase in diastolic pressure, however, was significant (P less than .05), but was entirely due to hypertension observed in six patients. Renography of these patients was normal. We conclude that the decrease in GFR observed during treatment with cisplatin is partly reversible. Cisplatin-treated patients have an increased risk of developing hypertension years after treatment.

Adult↗

The value of pre-scheduled bone scintigraphies in breast cancer.

During the first 10 years of Danish Breast Cancer Cooperative Group (DBCG), the subcommittee on bone scintigraphy has focused on the value of bone scintigraphy at the time of operation in all patients and then yearly in those considered to be primarily operable (stage I and II). Out of 1175 patients examined at time of operation, bone metastases could be verified by x-ray or histology in only 16, of whom the majority had bone pain and/or spread to other organs. Similarly, around 2.5% per year for the first 3 postoperative years and about 1% per year during the next 4 postoperative years had bone metastases verified by x-ray or histology within 12 months after the latest scheduled bone scintigraphy. It is concluded that bone scintigraphy is of no value in primarily operable patients with breast cancer, and that the examination should be reserved for patients with symptoms and/or signs of bone metastases and for patients with relapse.

Bone Neoplasms↗

Clinical and radiologic characteristics of bone metastases in breast cancer.

Metastatic bone disease was evaluated in 380 consecutive patients at the time of first metastasis of breast cancer. Studies included radiographic examination, radionuclide examination, and bone marrow biopsy. Radiographs of the skeleton demonstrated metastases in 120 patients (32%), and in 40 of these patients (13%) the bone was the only site of metastases. The diagnostic efficiency was 82% for bone scanning, 80% for pain evaluation, 59% for s-calcium analyses, and 77% for s-alkaline phosphatase analyses. Bone scanning is an effective method to exclude metastatic bone disease (sensitivity: 96%). A positive scan, however, requires radiologic confirmation (specificity: 66%). Bone scanning of the skeleton should be the initial staging procedure in all patients with recurrent breast cancer with no clinical or biochemical signs of bone metastases. Bilateral posterior iliac crest bone marrow aspirations and bone biopsies were positive in 82 out of the 320 patients who underwent biopsy. The frequency of positive bone marrow biopsy was significantly correlated with both the site of radiographic metastases and with the total number of involved bone regions. Routine bone marrow biopsies are indicated in patients with a positive bone scan, but a negative x-ray examination. In these cases biopsies should be performed bilaterally.

Biopsy↗

The presence of tumor cells in bone marrow at the time of first recurrence of breast cancer.

The occurrence of bone marrow carcinosis was investigated in 380 patients at the time of first recurrence of breast cancer. Results were related to results from radiographic bone survey, 99mTc MDP bone scintigraphy, clinical examination and serum alkaline phosphatase and serum calcium levels. Eighty-seven patients (23%) had tumor cells in the bone marrow. X-rays showed metastases in 78% of the patients with and in 16% of the patients without bone marrow carcinosis. The diagnostic efficiency of x-rays with bone marrow biopsy as the key diagnostic factor was 83%, and it was superior to that of other investigation methods. Bone tissue biopsies were positive alone in 15 patients (17%) and marrow aspirations were positive alone in seven patients (8%). Imprint preparations were positive alone in 7% of the patients and bone tissue biopsy in 5% of the patients. Heavy tumor infiltration (greater than or equal to 50%) of the bone marrow was associated with the occurrence of numerous regions of radiographically involved bone lesions and with histopathologic evidence of bone destruction. Furthermore, pronounced bone formation and marrow fibrosis were more commonly seen in patients with osteosclerotic bone metastases than in patients with osteolytic bone metastases. This study provides evidence that the primary soil of metastatic bone disease in human breast cancer is the bone marrow and that radiographic evidence of bone metastases is a result of an invasion and destruction of the bone tissue matrix by tumor cells from the marrow cavity.

Adult↗

Exaggerated postural vasoconstrictor reflex in Raynaud's phenomenon.

The central and local regulation of capillary blood flow in the finger was studied by the local xenon-133 washout technique in women with primary Raynaud's phenomenon, men with vibration induced white finger, and their respective sex matched controls. The vasoconstrictor response to venous stasis of 40 mm Hg elicited by local reflex was normal in both types of Raynaud's phenomenon. Change in posture from lying to sitting induced vasoconstriction in all groups, which was abolished by proximal nervous blockade. The vasoconstrictor response to sitting was augmented in both groups of subjects with Raynaud's phenomenon compared with their sex matched controls. These results show the existence of central and local postural vasoconstrictor reflexes in normal fingers. In both types of Raynaud's phenomenon there was hyperreactivity of the central sympathetic nervous system to orthostatic stress and normal function of digital arterioles and postganglionic sympathetic nerve fibres.

Adult↗

Incidence and methodologic aspects of the occurrence of liver metastases in recurrent breast cancer.

The occurrence of liver metastases was evaluated by ultrasonic scanning and correlated with prognostic factors, pattern of metastases, clinical examination, biochemical liver function tests from serum, and liver biopsy specimens in 394 consecutive evaluable patients with first recurrence of breast cancer. Fifty-nine patients (15%) had a positive scan, and liver metastases were the only sign of recurrent disease in 11 of these patients. The presence of liver metastases was not associated with age, menopausal status, size of the primary tumor, regional lymph node status, or the length of the recurrence-free interval; but patients with liver metastases were significantly closer to the menopause than those without (P = 0.02). The diagnostic value of clinical examinations was comparable to that of serum bilirubin and serum aspartate aminotransferase (ASAT) analyses, but was significantly better than alkaline phosphatase (AP) and lactate dehydrogenase (LDH) analyses. Analysis of serum AP was not a valuable diagnostic tool in the diagnosis of liver metastases, since it was elevated in 58% of the patients with bone metastases, and since metastases in this site were found in one third of the patients without liver metastases. If all four tests were negative, liver metastases were excluded in 99% of the patients, and if more than two of the four tests were positive, liver metastases were found in 95%. Valid (greater than 80%) diagnosis of liver metastases by serum LDH or serum ASAT alone, required an elevation of three or five times the upper normal limits, respectively. Thirty-nine patients with positive ultrasonography results underwent biopsy. The ultrasonographic diagnosis could not be confirmed histologically in three patients (8%). If ultrasonic scanning had not been performed routinely, only one of 213 patients (0.5%) with soft tissue metastases would have been offered local therapy rather than systemic treatment. These data suggest that ultrasonic scanning of the liver should not be a routine diagnostic tool in examination of patients with first recurrence of breast cancer. However, whenever indicated by clinical signs or elevated blood tests, scanning should be performed to confirm the presence of liver metastases, particularly in patients entering therapeutical trials, since liver metastases demonstrated by ultrasound examinations may serve as a measurable parameter.

Aspartate Aminotransferases↗

Nephrotoxicity of cyclosporin A in humans: effects on glomerular filtration and tubular reabsorption rates.

The contention that cyclosporin A (CyA) nephrotoxicity may be due to renal afferent arteriolar constriction was inferred from rat studies showing CyA to increase renal vascular resistance, to reduce glomerular filtration rate (GFR) and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle (Vprox), and to increase proximal fractional reabsorption. In order to test whether the mechanism of human CyA nephrotoxicity is similar to its rat analogue, and whether CyA treatment causes prolonged renal malfunction after drug withdrawal, renal function was investigated with clearance techniques including lithium clearance (CLi) as a measure of Vprox. The subjects were patients (n = 11) with previously normal renal function, given CyA in the treatment of ocular manifestation of extrarenal disease, or bone-marrow transplant recipients. Nine out of these eleven patients were investigated before and during CyA treatment: GFR (P less than 0.05) and Vprox (P less than 0.005) decreased while proximal fractional reabsorption increased (P less than 0.01). In six patients investigated before CyA was given, and re-examined a mean of 273 days (range 84-384 days) after CyA withdrawal, CLi was reduced (P less than 0.05) while mean GFR was not significantly lowered (0.5 greater than P greater than 0.2). In one of these six patients GFR was reduced to a subnormal value of 26 ml min-1 (1.73 m2 body surface)-1. In conclusion, human and rat CyA nephrotoxicity have the same pattern of renal functional deterioration. Cyclosporin A nephrotoxicity was evident in patients investigated a mean of 9 months after CyA withdrawal.

Absorption↗

Regional lung function impairment following post-operative radiotherapy for breast cancer using direct or tangential field techniques.

We have compared the effect of tangential and direct irradiation on regional lung function in 22 consecutive patients with breast cancer, who had been treated by post-operative irradiation 3 months prior to the examination. The tangential technique (total dose 32-36 Gy, less than 5 Gy of the lung) was employed in eight of the patients, while the direct technique (total dose 40 Gy, 5-20 Gy to the lung) was used in the other 14. In the group that had been treated by the tangential technique, there was no impairment of the ventilation or perfusion of the irradiated lung compared with the contralateral lung. The radiographs of the thorax were all normal. In the group that had been treated by the direct technique, there was a reduction in both the ventilation and the perfusion in 12 of the patients (p less than 0.01). The radiographs of the thorax were abnormal in only seven of these 12 patients. In both groups the regional leakiness of the lungs was evaluated as the pulmonary clearance of inhaled nebulised 99Tcm-DTPA. Due to differences in smoking habits between and within the groups, the results were not conclusive. It is concluded that the regional lung function was not significantly affected by the tangential technique, in contrast to a pronounced and harmful effect of the direct technique.

Aged↗

Steroid hormone receptors as prognostic indicators in primary breast cancer.

Recurrence-free survival (RFS) has been evaluated with regard to estrogen and progesterone receptor (ER and PgR) status for 145 postmenopausal women with primary breast cancer at high risk for recurrent disease. All patients received only local-regional therapy as an adjuvant therapy (DBCG protocol 77-c patients). ER+ patients had a significantly longer RFS than ER-patients. This difference was apparent using a cut-off level of 10 fmol/mg cytosol protein to distinguish between ER+ and ER-patients. There was no apparent difference in patients with high (greater than = 100 fmol/mg cytosol protein) ER levels vs. those with intermediate (10-99 fmol/mg cytosol protein) levels, indicating that the prognostic value of ER determinations in the natural course of the disease resides in a qualitative rather than a quantitative distinction among patients. No difference in RFS was found patients when patient were subdivided according to PgR status. The clinical applicability of the ER-ICA assay method for ER determinations is demonstrated in a subset of patients, some of whom received adjuvant endocrine therapy.

Actuarial Analysis↗

Carbon monoxide diffusing capacity: a reliable indicator of bleomycin-induced pulmonary toxicity.

Seventy-seven untreated patients with germ-cell tumors, of whom 20 had no pulmonary involvement, no clinical or radiological evidence of pulmonary disease, received 6 courses of cisplatin, vinblastine and bleomycin. Pulmonary function tests were performed before, every 3 weeks during treatment, and once a month from then on. The carbon monoxide diffusion capacity tests were normalized with respect to the actual hemoglobin concentration. During treatment a nonsignificant decrease (P greater than 0.05) was seen in the flow volume relationships, but as it was reversible it was attributed to the strenuous treatment. In contrast a significant decrease of 35% (P less than 0.01) in the corrected carbon monoxide diffusion capacity was seen in 15 of 18 evaluable patients with neither clinical nor radiological signs of pulmonary toxicity. The decrease was correlated to the increasing dose of bleomycin (r = 0.63).

Adolescent↗