Thyroid tumors following thymus irradiation

About 2,650 persons who received X-ray treatment for purported enlarged thymuses in infancy and 4,800 sibling controls have been followed by mail questionnaire for an average of 29 years to observe their incidence of thyroid tumors. The follow-up rate in the latest survey was 88% in both groups. The radiation doses to the thyroid gland ranged from 5 to over 1,000 rad, with 62% receiving less than 50 rad. To date 30 thyroid cancers and 59 benign thyroid adenomas have been detected in the irradiated group, as compared with 1 thyroid cancer and 8 adenomas in the control group. The relative risks in the irradiated group were about 45 for thyroid cancer and 15 for benign thyroid adenomas. The dose-response curve for thyroid cancer was essentially linear, although a linear-quadratic curve could not be ruled out. For thyroid adenomas the risk per rad was somewhat greater at lower doses than at high doses. For both thyroid cancers and adenomas the absolute excess risk per rad was two to three times as great in females as males. Within the limitations imposed by the treatment regimens and the sample size, there was no indication of a "sparing" effect due to dose fractionation for either thyroid cancers or adenomas. There was an excess risk for both malignant and benign thyroid tumors for at least 40 years post irradiation. For thyroid cancer the radiogenic risk appeared to be additive with respect to time, rather than the age-specific natural rates of cancer being multiplied.     

Meptazinol, a new analgesic. Hemodynamic and respiratory effects

In a prospective, randomized double-blind study the hemodynamic and respiratory effects of i.v. meptazinol, a new synthetic narcotic agonist-antagonist analgesic given in 2 dosages (2 mg/kg and 4 mg/kg), were compared over 15 min to a control group that received 0.9% saline solution as placebo. In a total of 80 patients scheduled for elective aortocoronary bypass surgery, the study was performed before and during general anesthesia and during extracorporeal circulation (ECC). A dose-dependent increase in mean arterial pressure (MAP) and total systemic resistance (TSR) were the predominant hemodynamic effects of meptazinol before and during anaesthesia (Tables 1 and 2). Within the study period no change in heart rate (HR) or cardiac index (CI) could be observed. Directly measured left ventricular parameters revealed a significant increase in left ventricular pressure (LVEDP, and dp/dtmax (Fig. 1). During ECC meptazinol injection was followed by a dose-dependent increase in perfusion pressure, indicating a direct vasoconstrictive effect; no influence on the capacitance system ("venous pooling") could be observed (Fig. 2). In the spontaneously breathing, premedicated patients (morphine hydrochloride 0.15 mg/kg and flunitrazepam 0.03 mg/kg) paO2 increased and paCO2 decreased, especially after injection of the higher dosage of meptazinol; there was no influence on intrapulmonary right-to-left shunting (Qs/Qt).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty

BACKGROUND: After total knee arthroplasty, patients regularly suffer from severe pain. It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief, patients' comfort and side effects. A new therapeutic approach, intraarticular opioids, has been suggested with the detection of opioid receptors in inflamed tissue. This method has proven suitable for clinical use in small operations (e.g. knee arthroscopy). In this study, we compared epidural analgesia and intraarticular application of morphine plus "on-demand" intravenous analgesia to "on-demand" intravenous analgesia alone. METHODS: Thirty-seven patients, scheduled for total knee arthroplasty, were randomly assigned to three treatment groups: in group 1 (EPI) patients received bolus doses of morphine via an epidural catheter; in group 2 (IA) an intraarticular bolus of 1 mg of morphine was applied at the end of the operation with subsequent use of a patient-controlled analgesia (PCA) pump; group 3 (Control), in which only PCA was provided, served as control for both analgesic procedures. Main outcome measures included visual analogue pain scales, total morphine consumption, and stress hormones. RESULTS: No statistically significant differences in visual analogue pain scales could be detected between the three groups. Application of intraarticular morphine did not reduce the amount of analgesics required for postoperative analgesia as compared to intravenous analgesia alone. Application of epidural morphine significantly suppressed beta-endorphine release, but did not significantly influence other stress hormones as compared to the control group. CONCLUSION: Epidural and intravenous analgesia after total knee arthroplasty are equivalent methods of pain relief. In major orthopaedic procedures, application of intraarticular morphine does not reduce analgesic requirements.     

Cerebral blood flow velocity and carbon dioxide vasoreactivity during gamma-hydroxybutyrate/fentanyl anaesthesia in non-neurosurgical patients

In this study the effects of gamma-hydroxybutyrate/fentanyl on cerebral blood flow velocity (CBFV) (as measured in the middle cerebral artery by transcranial Doppler ultrasonography) and on cerebrovascular carbon dioxide reactivity were investigated. Mean CBFV (Vmean) and haemodynamic responses were recorded in 12 non-neurosurgical patients before, during and after induction of general anaesthesia with gamma-hydroxybutyrate (GHB) (20 min constant rate infusion of 100 mg kg-1). Two patients were excluded, one because of bradycardia and the other because of severe myoclonia. During the infusion of GHB, normocapnia was maintained by manually assisting ventilation as necessary. The infusion of GHB did not affect Vmean [awake: 57 +/- 12 cm s-1 (mean +/- SD); 22.5 min: 62 +/- 15 cm s-1, NS difference] or mean arterial blood pressure (MAP) (awake: 97 +/- 12 mmHg; 22.5 min: 89 +/- 10 mmHg, NS). This suggests that cerebral blood flow velocity is unaltered by an anaesthetic dose of GHB. Twenty-five minutes after the start of GHB, fentanyl 3 micrograms kg-1 and vecuronium 0.1 mg kg-1 were given, the trachea was intubated and the lungs were mechanically ventilated to maintain end-tidal PCO2 of 4.6 +/- 0.4 kPa (30 min). At 30 min after the start of the GHB infusion, Vmean and MAP decreased to 38 +/- 10 cm s-1 and 76 +/- 12 mmHg (both P < 0.05 vs 22.5 min) respectively. After adjusting the ventilation to achieve hypocapnia (40 min: end-tidal PCO2 3.5 +/- 0.2 mmHg), Vmean decreased to 29 +/- 7 cm s-1, while MAP did not change. This allowed the relative vasoreactivity (percentage change in Vmean/0.133 kPa change in the end-tidal PCO2 from normocapnia to hypocapnia) to be estimated as 2.7 +/- 1.6% 0.133 kPa-1. This suggests that cerebrovascular response to CO2 during gamma-hydroxybutyrate/fentanyl anaesthesia is maintained.     

Does the technique of cardiopulmonary bypass affect lung water content?

Several efforts have been made to improve the technique of cardiopulmonary bypass (CPB), including the use of pulsatile flow and the modification of cannulation technique. The present study focused upon extravascular lung water (EVLW) in 60 aortocoronary bypass patients subjected to four different perfusion techniques during CPB: group 1 (n = 15): non-pulsatile flow and standard cannulation; group 2 (n = 15); pulsatile flow and standard cannulation; group 3 (n = 15): nonpulsatile flow and monoatrial cannulation (i.e., always "partial" bypass during CPB); group 4 (n = 15): pulsatile flow and monoatrial cannulation. EVLW content was measured using the double-indicator dilution technique with indocyanine green; in addition, various hemodynamic and laboratory variables were measured. Lung water content rose above normal values (mean: 5.79 +/- 0.33 ml/kg) only in the groups submitted to the standard cannulation technique, irrespective of whether the perfusion flow was pulsatile or not (group 1: + 27.4%; group 2: + 25.5%). Pulmonary gas exchange, too, was compromised only in these patients (PaO2 in group 1 -19% and in group 2 -17%; Qs/Qt in group 1 + 36 rel. % and in group 2 + 29 rel. %), whereas all patients with monoatrial cannulation and partial bypass throughout the CPB period showed no rise in EVLW content or Qs/Qt and no drop in PaO2. From the results of this study we conclude that pulsatile perfusion during open heart surgical procedure has no advantages in regard to lung water content. Monoatrial cannulation with partial bypass at all times during CPB, however, seems to be beneficial, probably owing to the maintenance of pulmonary circulation during the bypass period.     

Renal accumulation of ammonia: the cause of post-ischaemic functional loss and the "blue line"

The "blue line", a dark discoloration at the corticomedullary junction, is a constant finding after a significant period of renal ischaemia. In this study, it has been shown to be caused by packing of all of the peritubular capillaries at the corticomedullary junction with red blood cells. Five rats and 10 dogs were alkalinised by replacing their drinking water with 2% sodium bicarbonate for 2 weeks pre-operatively, in order to inhibit the glutaminase enzyme system and thereby decrease ammonia accumulation during ischaemia. Five rats and 6 dogs were used as unprotected controls. All animals were subjected to 60 min warm ischaemia. Renal function was significantly protected in the alkalinised rats (P less than 0.002) and dogs (P less than 0.001), with the serum creatinine rising to a maximum of 0.21 +/- 0.03 mmol/l in the alkalinised rats and 0.18 +/- 0.04 mmol/l in the alkalinised dogs. There was no "blue line" in the alkalinised animals. It is suggested that the "blue line" plays a central role in post-ischaemic renal failure. Prevention of ammonia formation by alkalinisation protects against ischaemic renal damage and the formation of the "blue line".     

Extrarenal effects of potassium-canrenoate. Haemodynamic investigations during neuroleptanalgesia in cardiosurgical patients (author's transl)]

Direct cardiac and vascular effects of the antikaliuretic diuretic potassium-canrenoate were measured in cardio-surgical patients during extracorporal circulation and immediatly after operations, each time in neuroleptanalgesia. During "steady state" extracorporeal circulation (aorta cross-clamped, constant flow rate of heart-lung-machine, constant hypothermia), in 13 patients no significant influence on peripheral circulation was found after i.v.-injection of 800 mg potassium-canrenoate. Neither arterial perfusion pressure (representing an arterial vascular reaction) nor changes in oxygenator-volume (indicating venous vasodilation or contraction) demonstrated significant differences in comparison to a control group. After cardiac surgery haemodynamic measurements were performed for a period of 60 minutes in 10 patients given 800 mg potassium-canrenoate. In comparison with a control group (n = 6), no significant differences in arterial pressure, heart rate, cardiac index and pulmonary arterial pressure were found. Left ventricular measurements, using a catheter tip manometer, revealed no direct positive inotropic effect of a single i.v.-injection of potassium-canrenoate. In acute myocardial failure during anaesthesia or in "low cardiac ouptut" following open heart surgery no improvement in myocardial contractility is obtained by i.v.-application of potassium-canrenoate; at the present there seems no alternative to other positive inotropic agents such as calcium, glucagon, dopamine, orciprenaline and epinephrine.