Reflections on medical oncology: an appeal for better clinical trials and improved reporting of their results.
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Biomedical subjects
Publications and source records attributed to K Murphy.
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1. The ventilatory response to electrically induced ;exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to ;exercise' were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions.2. Phasic hind limb ;exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact.3. Cord transection produced no significant change in either the resting values of ventilation ( V(I)) and CO(2) production ( V(CO) (2)) or the ventilatory equivalent for CO(2) during ;exercise' ( big up tri, open V(I)/ big up tri, open V(CO) (2)).4. During the steady state of exercise P(a, CO) (2) was on average significantly lower than at rest with the cord intact (mean big up tri, openP(a, CO) (2), - 2.1 mmHg; range - 5.7 to + 1), and higher, though not significantly, with the cord cut (mean P(a, CO) (2), + 1.2 mmHg; range - 1.5 to + 4.3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO(2) sensitivity; the big up tri, open V(I)/ big up tri, openP(a,CO) (2) obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO(2) inhalation (true sensitivity) both before and after cord section.5. V(I) and V(CO) (2) increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection.6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced ;exercise' was free of artifact.7. It was concluded that spinal cord transmission is not necessary for the steady-state ventilatory response to electrically induced exercise of the hind limbs.8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise.
1. The effect of electrically induced ;exercise' on the respiratory oscillation of arterial pH was studied in chloralose-anaesthetized dogs with spinal cord transection at T8/9 (dermatome level T6/7).2. Respiratory oscillations of arterial pH (presumed to be due to oscillations of arterial P(CO2)) were sensed with a fast-responding electrode in one carotid artery. Breath-by-breath estimates of the maximum rate of change of pH of the downstroke of the pH oscillation (dpH/dt downward arrowmax) were obtained by differentiating the pH signal.3. Consistent with the findings of the previous paper (Cross et al. 1982), the ventilatory response to exercise could not be explained on the basis of sensitivity to CO(2); the Delta V(I)/DeltaP(a, CO2) was significantly greater for ;exercise' than for CO(2) inhalation.4. On average, the amplitude of the pH oscillations decreased during ;exercise'. The change in the phase relationship (varphi) between respiratory and pH cycles, although significant from the second breath onwards, was not thought to be responsible for the increased ventilation V(I); the direction of the change was opposite to that previously found to increase V(I).5. Inspiratory duration (t(i)), expiratory duration (t(e)), V(I) and the dpH/dt downward arrowmax changed significantly by the third breath of ;exercise'. A significantly linear relationship was obtained between t(e) and dpH/dt downward arrowmax during the on-transient (first ten breaths) of ;exercise'. This relationship was maintained throughout ;exercise'. V(I) and dpH/dt downward arrowmax were also linearly related during the on-transient, although the same relationship did not hold true throughout ;exercise'.6. The dpH/dt downward arrowmax was related to CO(2) production ( V(CO2)) lending support to the prediction that the slope of the downstroke of the pH oscillation is a function of V(CO2).7. It was concluded that the dpH/dt downward arrowmax (dpCO(2)/dt upward arrowmax) is a potential humoral signal in ;exercise' and could account totally for the shortening of t(e). Since there was a late rise in V(I) (due to an increase in tidal volume V(T)) in the absence of a change in dpH/dt downward arrowmax, it was considered unlikely that the dpH/dt downward arrowmax was the only humoral signal present during ;exercise'.
Among the problems encountered today in Expanded Programmes on Immunization (EPI) is the failure to reach an acceptable level of immunization coverage in rapidly growing urban areas. This paper describes a checklist to identify the reasons for such low coverage. The checklist was first used in Yaounde, United Republic of Cameroon. There the low coverage is found to be associated with certain neighborhoods, one ethnic group, low socio-economic status, and newly-arrived families. Publicity about immunizations is not reaching Yaounde residents in those categories. Furthermore, health lessons (given only in French) seem to be confusing the parents rather than educating them. Finally, previous ineffective immunization programmes have made Yaounde residents mistrustful of the current programme. The authors recommend solutions to each of these Yaounde problems. The checklist, and the methods used for answering it in Yaounde, should prove useful to other immunization programmes.
Leiomyosarcoma, a highly malignant tumor of the inferior vena cava, is rare. Only 55 cases have been reported in the world literature, and of these only 18 were evaluated with a special vascular procedure, either arteriography or inferior vena cavography. In two cases of leiomyosarcoma of the inferior vena cava, we performed arteriography and inferior vena cavography. In one, computed tomographic studies were also carried out. Cavography showed a lobulated filling defect in one case and complete caval occlusion with collateral circulation in the other. In the one case in which it was performed, computed tomography clearly demonstrated the tumor's size and its relationship to surrounding organs. Arteriographic studies, however, allowed only an indistinct delineation of the extent of tumor growth in one case. Venography followed by computed tomography should permit adequate assessment of most leiomyosarcomas of the inferior vena cava, with arteriography reserved for tumors involving the upper cava in which hepatic involvement must be evaluated.
Previous studies on the duration of antibody following vaccination with 17D yellow fever (17D YF) virus vaccine have indicated that immunity persists for at least 17 years and suggest that the vaccine may provide lifelong immunity. We studied sera obtained from 149 veterans of the Second World War, 30 - 35 years after military service during which YF vaccination was required for defined groups. A significantly high proportion of "vaccinated" subjects was found to be seropositive to 17D YF virus. The highest proportion of seropositive "vaccinated" veterans (97%) was among navy and air corps personnel, while only 60% of "vaccinated" army personnel and 19% of "unvaccinated" personnel were seropositive. This study suggests that (i) antibody to 17D YF virus, as measured by the plaque-reduction neutralization test (PRNT), persists for 30 years or more following administration of a potent vaccine; (ii) army personnel often had not received potent vaccine, even though their service history indicated that they should have been vaccinated; (iii) some personnel were vaccinated, although their service did not include vaccination-designated areas; and (iv) 88% of veterans with persistent PRNT antibody to 17D YF virus also had mouse-protective antibody against French neurotropic YF virus.
Seven hundred patients at a community hospital underwent gastric bypass for morbid obesity. Postoperative complications developed in 14.9 percent. The incidence of major complications was particularly low. Both weight loss and the percentage of excess weight lost in the postoperative period were very satisfactory. The criteria for selecting patients for gastric bypass are presented and preoperative evaluation is reviewed. Major technical points in the operation are stressed. Roux-Y reconstruction of gastrointestinal continuity is the preferred technique in our hands. This report reemphasizes the safety and efficacy of gastric bypass as a treatment for morbid obesity. When careful patient selection, preoperative evaluation and operative techniques are combined. excellent results can be expected in the community hospital.
We measured the regional distribution of pulmonary extravascular and interstitial water to examine the possibility that regional differences in microvascular pressure or tissue stress may cause regional differences in lung water. We placed chloralose-anesthetized dogs in an upright (n = 6) or supine (n = 7) position for 180 min. We injected 51Cr-labeled EDTA to equilibrate to the extracellular space and 125I-labeled albumin to equilibrate with plasma. At the end of the experiment, the lungs were removed, passively drained of blood, and inflated before rapid freezing. Lungs were divided into horizontal slices, and extravascular, interstitial, and plasma water, red cell volume, and dry lung weight were determined for each slice. We found that regional extravascular and interstitial water were constant throughout the lungs in both groups and that there were no significant differences between upright and supine dogs. There were no significant differences in hematocrit between slices. We conclude that gravity and body position have no measurable effect on either the total size of the extravascular and interstitial compartments or their regional distribution.
Diazepam, in moderate doses, has been used in a placebo controlled, single blind study to treat dyspnoea in four patients severely disabled from chronic airflow obstruction. The subjects had the 'pink puffer syndrome', usually associated with emphysema and were not hypercapnoeic nor severely hypoxic at rest. With diazepam, they experienced a striking reduction in dyspnoea, and an improvement in effort tolerance; in addition the slope of the ventilation/CO2 response curve was reduced. There were no changes in resting blood gases. Psychiatric examination at the end of the study did not reveal prominent anxiety, although three patients were depressed. The use of diazepam to treat dyspnoea in this syndrome is safe in the absence of any acute infection
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Pseudomonas osteochondritis of the chest wall and sternum has rarely been reported, but when present it has been extremely difficult to eradicate. Multiple operations to debride the involved areas and use of antibiotics have often been inadequate to control this resistant infection. This report describes our experience with three patients who had the late development of Pseudomonas osteochondritis of the chest wall. The infection occurred following crush trauma, sternotomy for congenital heart disease, and mastectomy and amputation of the upper extremity for carcinoma of the breast. Antibiotic therapy alone and with limited operations was unsuccessful in controlling the infection in all three instances. Eventually, each patient required extensive regional surgical removal of involved bone and cartilage. Complete healing followed. Our experience favors the early wide removal of bony and cartilaginous tissues in the involved region with preoperative and postoperative coverage by appropriate antibiotics. Operative management is detailed.
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Ultrastructural, histopathologic, and virologic studies of adult hamsters infected with virulent Venezuelan equine encelphalomyelitis (VEE) virus (Subtype I-B) demonstrated precise chronologic and topographic progression of lesions and viral replication in extraneural sites. Thymus contained the earliest lesions and the highest initial and subsequent viral titers. No particular cytotropism was observed as highly efficient viral replication and severe cytonecrosis proceded. Early cortical necrosis of splenic periarteriolar lymphocytic sheath was followed by lymphoblastoid repopulation of the peripheral zone. Massive bone marrow necrosis was accompained by ultrastructural evidence of VEE viral particle production in reticulum cells, rubricytes, myeloid cells, lymphoblastoid cells, and megakaryocytes. Speed, efficiency, destructiveness, and relative sensitivity of virtually all lymphoreticular and hematopoetic cells were hallmarks of virulent VEE infection in the hamster.
It was not possible to demonstrate an increase in the proportion of goblet cells in the bronchioles of patients with chronic bronchitis and no emphysema, whereas other lesions, such as mucous gland hyperplasia, airway narrowing, and airway mucus were easily demonstrated in similar cases. Thus, it seems that goblet cell metaplasia is not an important factor in patients who have chronic bronchitis but little evidence of chronic airflow obstruction. Goblet cell metaplasia is an obvious feature of patients with chronic bronchitis and emphysema, especially in those with symptomatic or fatal chronic airflow obstruction, and it may be responsible for producing obstruction in the peripheral airways of these subjects. The role of goblet cell metaplasia in smokers with little airflow obstruction is uncertain from the data presented. No difference was noted in the proportion of goblet cells between bronchitic patients and nonbronchitic smokers who did not have clinical airflow obstruction.
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