Intratumoral distribution of microspheres

Fifteen mu carbonized microspheres injected in two transplantable rat tumors, a hepatoma transplanted to the dorsum of one hindpaw and an adenocarcinoma transplanted into the liver, were found to be unevenly distributed and often in aggregates that seemed to fill intratumoral vessels. This finding can partly explain the increased vascular resistance in tumors after microsphere injection and makes the technique with repeated injections of microspheres disputable.     

Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP)

OBJECTIVE: To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis. METHODS: Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models. RESULTS: The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes. CONCLUSIONS: There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions.     

The Gothenburg Breast Screening Trial

BACKGROUND: Although there is evidence for a reduction in breast carcinoma mortality with mammographic screening, some doubts have been expressed, and there is still uncertainty regarding the age specific effects. METHODS: The authors report on a randomized, controlled trial of mammographic screening for breast carcinoma that was conducted among 51,611 women (21,650 women who were invited to a screening [the study group] and 29,961 women in a control group) ages 39-59 years in Gothenburg, Sweden. Among women in the study group, the screening interval was 18 months. The screening phase of the trial took place in 1982-1991, and follow-up for breast carcinoma mortality continued until December 31, 1996. Mortality from breast carcinoma was analyzed using a Poisson regression model. Overall and age specific effects of invitation to mammography screening on breast carcinoma mortality were calculated. Three mortality effects were estimated: the effect on deaths from breast tumors diagnosed during the screening phase of the trial, as assessed by an independent Endpoint Committee (the EPC evaluation model); the effect on deaths from breast carcinoma diagnosed during the screening phase of the trial, as determined by data from the National Cancer Registry and the National Cause of Death Register (the SCB evaluation model); and the effect on deaths from all breast carcinomas diagnosed up to December 31, 1996, as determined by the National Cancer Registry and the National Cause of Death Register (the SCB follow-up model). RESULTS: A nonsignificant, 21% reduction in the rate of mortality from breast carcinoma with invitation to screening was observed using the EPC evaluation model (relative risk [RR], 0.79; 95% confidence interval [95% CI], 0.58-1.08; P = 0.14); and a borderline significant, 23% rate reduction was observed using the SCB follow-up model (RR, 0.77; 95% CI, 0.60-1.00; P = 0.05). Age specific analyses yielded greater mortality rate reductions for the groups of women ages 39-44 years, 45-49 years, and 55-59 years, but there was no mortality rate reduction in the group of women ages 50-54 years. The effects of invitation to mammographic screening on the incidence of lymph node-positive disease closely paralleled the effects of invitation on breast carcinoma mortality. The effect on breast carcinoma mortality was consistent with the effect on all-cause mortality, suggesting no bias in classification of cause of death. Breast carcinoma incidence in the study group was almost identical to the incidence in the control group after trial by screening had ended in the control group (RR, 0.98; 95% CI, 0.88-1.09; P = 0.7). CONCLUSIONS: The current results support the commonly observed 20-30% reduction in breast carcinoma mortality with invitation to screening. The impression that screening is less effective in women younger than 50 years may be an oversimplification. Age specific effects should be a target for further research.     

Nicotine delays arousal during hypoxemia in lambs

A decreased ability to arouse from sleep in response to arterial hypoxemia may lead to severe asphyxia and has been proposed as a mechanism of sudden infant death syndrome. Based on previous observations that nicotine exposure, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infusion of nicotine could impair hypoxic arousal through interference with oxygen-sensing mechanisms. Seven chronically instrumented unanesthetized lambs were studied at the age of 4.6 +/- 1.3 d during normoxia and acute hypoxia (0.1 fraction of inspired oxygen) for 5 min. Ventilation, transcutaneous Hb oxygen saturation, blood pressure, heart rate, and time to arousal were compared during a control saline infusion and during a 0.5 microg x kg(-1) x min(-1) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as well as arousal, were defined by EEG, nuchal electromyogram, and electrooculogram. Each lamb acted as its own control. Arousal from quiet sleep occurred significantly later during nicotine infusion compared with control (177 +/- 93 versus 57 +/- 41 s, p < 0.01) and at a lower transcutaneous Hb oxygen saturation (60 +/- 12 versus 79 +/- 12%, p < 0.01) (paired t test). The ventilatory response to hypoxia in wakefulness was similar during both conditions but was significantly attenuated in quiet sleep during nicotine infusion (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and heart rate responses were similar during both conditions. These results suggest that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance for sudden infant death syndrome.     

Methods for evaluation of postural control adaptation

New methods were developed to determine the dynamic changes of postural control during the initial exposure to large perturbances of stance. The adjustments of postural control over time in measured anteroposterior torque, were investigated in ten normal subjects. Perturbations of stance were evoked by two high intensity vibrators applying pseudorandom stimulation either to the calf muscles or the paravertebral muscles of the neck. The new methods use a system identification approach, which distinguishes between feedback control, adaptation of postural responses and adaptation to stimulus. This approach makes it possible to quantify motion dynamics and complexity, stimulus impact and adjustments of postural control. Quantification of the different adaptive responses could be useful for diagnostic purposes, in evaluating treatment efficacy and patient progress in rehabilitation programs.     

Selective celiac angiography and surgical exploration for suspected liver cancer: A comparative study of 196 patients

In 196 patients subjected to celiac angiography and exploratory laparotomy for suspected liver tumor, 81 per cent of the tumors were diagnosed by angiography, 26 per cent of patients had false-negative angiograms, and 16 per cent had false-positive angiograms. Diagnosis on laparotomy proved correct except in one patient. Of 22 patients with liver tumors not diagnosed on angiography, 10 could be specifically treated and 3 of them have survived more than one year. This gain is discussed in relation to the rather high number of unnecessary laparotomies.     

A scintillation camera technique for measurements of the reticuloendothelial function —Comparison of different methods for measuring RES function

A highly standardized ^99mTc-sulphur colloid was used to evaluate reticuloendothelial system (RES)-function in the normal rat and after RE blockade by gelatin (Haemaccel). Activity distribution in the animals was measured with a scintillation camera technique. Total uptake of activity in the liver was estimated. From the time-activity curves over the liver, the phagocytic index (k _phag) was evaluated. Estimation of the uptake rate of the labelled colloid into the liver and into other parts of the RES was also performed using a twocompartment model. Different methods of evaluation of RE function were compared. It was shown that for a proper estimation of the RE function, the whole uptake curve must be considered. Gelatin (Haemaccel) significantly reduced the total colloid uptake by the liver. The colloid uptake rate into the liver was also significantly reduced. Liver specimens after colloid injection were examined by light and electron microscopy showing vacuolation of hepatocytes and sinusoidal cells probably due to pinocytosis. The technique described enables functional studies of the RES. It has the advantage of noninvasive registrations and is based on the same technical facilities as used for routine liver scintigraphy.     

Balance control and adaptation during vibratory perturbations in middle-aged and elderly humans

The objective was to investigate if healthy elderly people respond and adapt differently to postural disturbances compared to middle-aged people. Thirty middle-aged (mean age 37.8 years, range 24–56 years) and forty healthy elderly subjects (mean age 74.6 years, range 66–88 years) were tested with posturography. Body sway was evoked by applying pseudorandom vibratory stimulation to the belly of the gastrocnemius muscles of both legs simultaneously. The tests were performed both with eyes open and eyes closed. The anteroposterior body sway was measured with a force platform and analyzed with a method that considers the adaptive changes of posture and stimulation responses. The results showed that middle-aged people generally used a different postural control strategy as compared to the elderly. The elderly responded more rapidly to vibratory perturbation, used more high-frequency (>0.1 Hz) motions and the motion dynamics had a higher degree of complexity. Moreover, the elderly had diminished ability to use visual information to improve balance control. Altogether, despite having an effective postural control adaptation similar to that of middle-aged people, the elderly had more difficultly in withstanding balance perturbations. These findings suggest that the balance control deterioration associated with aging cannot be fully compensated for by postural control adaptation.