Biomedical subjects
Publications and source records attributed to C Mercke.
Subcutaneous metastases from an oesophageal carcinoma were irradiated using different schedules. The results have to be evaluated with greatest caution but indicate that with the same CRE value, few fractions caused less skin reactions than several, and the size of the shoulder of the cell survival curve was of the order of 0.7 Gy.
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The results and side effects of en-bloc irradiation of ear, nose and throat tumours and their lymphatics showed that the technique had been successful in nasopharyngeal carcinoma, but poor in carcinoma of the hypopharynx. Marked early and late radiation side effects were relatively common in high age and with certain tumour sites, whereas no correlation could be demonstrated with total absorbed dose, fractionation, cumulative radiation effect or major surgery.
Patients with unresectable or inoperable bronchial carcinoma were treated with en-bloc irradiation of the tumour and the mediastinal lymph nodes to a total target absorbed dose of 40 Gy in 20 fractions. The first 52 patients were treated in one series and the last 45 patients in two series (split-course). Radiation adverse effects were only mild. The two regimens gave the same palliative results. The median survival was the same for the 2 groups (8 months). Most patients died in disseminated disease.
Endogenous production of carbon monoxide (VCO), total and direct reacting serum bilirubin (TSB, DRB) were determined in 26 patients with liver cirrhosis and portal hypertension to evaluate the effect of various shunt operations on total heme catabolism. The material was divided into 3 groups. In group I, 11 patients not operated upon, mean VCO (+/- S.D.) was 18.4 +/- 6.0 micronmol/mmol total body heme per day (reference value 12.6 +/- 2.9). In group tii, 7 patients operated upon with subcutaneous transposition and a subtotal resection of the spleen, mean VCO (14.4 +/- 4.7) was not significantly raised. In group III, 8 patients operated upon with a modified distal splenorenal shunt, the highest mean VCO (26.1 +/- 9.0) was found. Mean TSB in the three groups was 34.8 +/- 29.2, 11.2 +/- 3.0, and 46.4 +/- 41.0 micronmol/l, respectively, and mean DRB 18.2 +/- 20.8, 3.7 +/- 1.0, and 26.8 +/- 34.1 micronmol/l, respectively. Estimated from preoperative laboratory values there was no difference in liver function between the three groups. The conclusion drawn is that heme catabolism, increased by 50% in liver cirrhosis complicated by portal hypertension probably due to a slight decrease in erythrocyte survival, tends to normalize after subcutaneous transposition and subtotal resection of the spleen. After spleno-renal shunting, on the other hand, a further increase in heme catabolism is seen. And so the increase in serum bilirubin often seen after the latter type of surgery is mainly related to a raised bilirubin production and not to a further decrease in liver function.
Endogenous production of carbon monoxide (VCO), red cell survival and iron kinetics were studied in 15 subjects with Hodgkin's disease. The subjects were divided into two groups, namely: eight patients with anaemia (group A, haemoglobin (Hb) concentration less than 11.5 g/dl) and seven patients without anaemia (group B, Hb concentration greater than 11.5 g/dl). Red cell survival was not significantly different in the two groups being 91 +/- 40 days (mean +/- 1 SD) in group A and 111 +/- 54 days in group B. Relative VCO (mumol/mmol total body haem (TBH/d) was, however, significantly higher (0.01 greater than P greater than 0.001) in group A (20.7 +/- 4.7) compared to group B (12.0 +/- 3.8). When absolute VCO (mumol/d) was compared to the daily turnover of circulating red cell haemoglobin haem (Vhaem-c), the VCO/Vhaem-c quotient was 2.1 +/- 0.9 in group A and 1.2 +/- 0.3 in group B. Erythron turnover of iron (ET, mumol Fe/mmol TBH/d) was calculated through subtraction of the non-erythron turnover (NET) from the total plasma iron turnover (PIT). ET was significantly higher (0.05 greater than P greater than 0.01) in group A (39 +/- 21) than in group B (20 +/- 8). The conclusion drawn from the finding of significant increases in VCO and ET without and concomitant significant decrease in red cell survival in the anaemia group is that ineffective erythropoiesis, i.e. bone marrow haemolysis, seems to play an important role in the anaemia of Hodgkin's disease.
Total haem catabolism has been studied through measurement of endogenous production of carbon monoxide (VCO) in 19 patients treated for breast carcinoma. The subjects were divided into three groups. Group A included six patients with haemoglobin (Hb) concentration greater than 11.5 g/dl and considered free from disease. Group B consisted of seven patients with distant metastases and Hb concentration greater than 11.5 g/dl and group C of six patients with distant metastases and anaemia (Hb concentration less than 11.5 g/dl). VCO in group A was 10.3 +/- 3.7 (mean +/- 1 SD) and in group B 9.0 +/- 2.5 mumol/mmol total body haem (TBH)/d. These values are not different from our normal values of 10.8 +/- 2.8 mumol/mmol TBH/d. In group C VCO was 21.1 +/- 3.1 (an increase of 100%). VCO was compared to daily catabolism of circulating red cell haemoglobin haem (Vhaem-c) in the VCO/Vhaem-c quotient. Vhaem-c was calculated from total circulating red cell haemoglobin haem (TBHb-c) and red cell survival. In group A and group B this quotient was 1.3 +/- 0.6 and 1.1 +/- 0.2, respectively, and in group C was 2.5 +/- 0.9. The difference between group A and B on one side and group C on the other side was significant (P less than 0.001). The 'extra' CO produced in patients with anaemia and disseminated disease (group C) was thought to originate from increased turnover of bone marrow haem, reflecting considerable ineffective erythropoiesis with destruction of haemoglobinized immature red cells. The results confirm earlier findings of a high VCO/Vhaem-c quotients in patients with anaemia secondary to Hodgkin's disease.
Erythrocyte filterability, reticulocyte count, total serum bilirubin, and CO hemoglobin percent saturation (COHb) were measured throughout one menstrual cycle in 17 women. The filterability was significantly depressed during the progesterone phase compared with the estrogen phase. The depressed filterability was accompanied by significant increases in reticulocyte count, total serum bilirubin, and COHb. Significant correlations were seen between filterability, reticulocyte count, and total serum bilirubin. However, COHb did not correlate significantly with any of the other variables studied. This is probably due to increased ventilation during the progesterone phase balancing the increased endogenous production of CO. It is possible that cyclic variations in heme turnover are related to changes in erythrocyte characteristics during the progesterone phase.
The endogenous production of carbon monoxide (VCO) has been followed with the aid of a rebreathing system for 3 hours in four healthy volunteers after i.v. injection of 50 mg nicotinic acid (NA). After an initial slight decrease for 15-30 min in the CO hemoglobin per cent saturation (COHb), a rapid increase was registered for 120 min, whereafter the VCO returned to the normal preinjection level. The amount of "extra" CO produced varied between 4.1 and 2.2 ml, corresponding to 2.9 and 1.6 g Hb or 182 and 98 mumol heme,respectively. These figures are 3-5 times higher than those reported in the literature, calculated from increases in serum iron, bilirubin and COHb (without the use of a rebreathing system). When related to the total body heme (TBH) estimated with the CO dilution technique, the amount of "extra" heme metabolized after NA corresponded to 0.30% (range 0.26-0.32) of the TBH (a fourth of the total daily heme turnover or a third of the daily HB heme catabolism.
Carbon monoxide production (VCO) total body heme (TBH) and serum bilirubin (SB) have been determined in healthy young men before and after 100 mg phenobarbital (10 subjects), 15 mg diazepam (7 subjects) and 75 mg oxazepam (7 subjects), respectively, daily for seven days. None of the drugs had any significant effect on VCO. SB and TBH were also unaffected. Baseline VCO (mean +/- 1 S.E.M.) was 12.6+/-0.6 mumol/mmol TBH and day. The postdrug VCO was 15.1+/-1.8, 14.1+/-1.4 and 14.7+/-1.5 after phenobarbital, diazepam and oxazepam, respectively. The corresponding values for SB were 5.4+/-0.8, 6.0+/-1.5 and 6.2+/-1.0 mug/ml, compared to a baseline value of 6.6+/-0.8 mug/ml. However, when the pooled postdrug data were compared with the pooled baseline values, mean VCO showed a probably significant increase (from 12.6+/-0.6 to 14.7+/-1.0 mumol/mmol TBH and day (p less than 0.05). It is concluded that although phenobarbital is known to increase the hepatic heme turnover, this effect is not measurable in terms of total heme turnover, no more than 20% of which comes from the liver.
Endogenous production of carbon monoxide (VCO), serum bilirubin (SB) and reticulocyte (retic) count have been followed during the menstrual cycle in 12 women (4 of them smokers) without contraceptive drugs and in 10 women (5 of them smokers) on contraceptive drugs. During the progesterone phase (Pph), VCO in the non-smokers was 18.2 +/- 2.1 mumol/mmol total body heme (TBH) and day (mean +/- 1 S.E.M.), compared with 10.1 +/- 1.0 during the estrogen phase (Eph). In the smokers, VCO was 10.4 +/- 1.9 during Pph and 12.5 +/- 0.7 during Eph. SB for the non-smokers was 5.2+/- 1.0 mug/ml during Pph and 3.9 +/- 0.5 during Eph, compared with 3.2 +/- 0.8 and 3.9 +/- 1.2, respectively, for smokers. The retic count for the non-smokers was 64.1 +/- 4.7 times 10(3)/mul during Pph and 17.7 +/- 5.1 during Eph. In the smokers the corresponding counts were 93.6 +/- 15.9 and 60.8 +/- 7.6. These results confirm earlier reports that VCO is increased during Pph and indicate that the rise could be due to a change in red cell catabolism, since it is concomitant with a significant increase in retic counts, which has not been found in earlier works on VCO, but which is known from reticulocyte studies. Furthermore, the results may indicate that persistent smoking affects the metabolism of CO and/or heme, since the smokers did not react with any change in VCO during Pph. In subjects using contraceptive drugs, VCO was significantly higher (14.9 +/- 0.6 on combined estrogen-gestagen drugs and 14.5 +/- 1.1 on continuous gestagens, respectively) than during Eph in non-smokers (10.1 +/- 1.0 mumol/mmol TBH and day), which might be taken as the baseline group. This indicates that the increased VCO in subjects on contraceptive drugs may be related to the activity of gestagens, which were concluded in all contraceptive drugs tested.
The endogenous production of carbon monoxide (VCO) and total serum bilirubin (SB) have been followed in five healthy male volunteers during one baseline day and one day with no caloric intake. VCO in the morning studies was 11.2+/-1.7 (mean +/-1 S.E.M.) on the baseline day and 10.1+/-2.3 mumol/mmol total body heme (TBH) and day on the fasting day, respectively. In studies before noon, VCO increased significantly on both days, to values of 17.8+/-1.6 and 19.6+/-2.2 mumol/mmol TBH and day, respectively. In the first study in the afternoon, VCO differed significantly between the two days, amounting to 12.1+/-3.0 and 23.7+/-3.5 on the baseline and the fasting day, respectively. The difference was still significant in the evening, when VCO was 11.6+/-3.1 and 22.1+/-4.9 mumol/mmol TBH and day. SB followed the same pattern, with mean values of 4.0+/-0.3, 4.9+/-0.3, 4.2+/-0.9 and 3.0+/-0.3 mug/ml during the baseline day and 4.5+/-0.6, 5.4+/-1.2, 7.0+/-0.5 and 8.5+/-1.0 mug/ml, respectively, during fasting day. Only insignificant amounts of conjugated bilirubin were found. The studies confirm earlier reports on the effect of caloric restriction on VCO. Since this effect is simultaneous with an increase in SB, it is concluded that the changes are secondary to an increase in total heme catabolism. They might be due to an increase in intracellular hepatic heme turnover but it cannot be excluded that starvation affects erythropoiesis and/or red cell catabolism, thereby causing an increase in VCO and SB.
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