Methylprednisolone and cortisol metabolism during the early post-renal transplant period

Despite the widespread use of methylprednisolone and the well-appreciated effects of this drug on HPA suppression, little data is available which describes individual patient exposure to both methylprednisolone and cortisol following renal allograft placement. The clinical utilization of methylprednisolone during the early post-transplant period is based upon standardized dosing protocols that do not consider factors which may influence the pharmacokinetics of this drug during the post-transplant period. Therefore, this study was designed to examine the pharmacokinetics of methylprednisolone (mean dose: 28 mg) and cortisol pharmacodynamics in 9 renal transplant recipients (4 females; 5 males) who were studied during the early post-transplant period (5 to 12 days after surgery). All patients (mean serum creatinine: 1.4 +/- 0.3 mg/dl) had serial blood samples collected over a 12- to 24-hour period (depending upon the dosing schedule) which were analyzed concurrently for methylprednisolone and cortisol. A three-fold variation in drug clearance ranging from 174 to 638 ml/h/kg with a range in the volume of distribution of 0.83 to 2.24 l/kg and resultant half-lives ranging from 1.20 to 3.02 hours was noted. The cortisol response was quantitated by a 12-hour cortisol area under the curve (C-AUC12) to examine the interpatient cortisol patterns during the early post-transplant period. C-AUC12 ranged from 44.0 to 636 ng.h/ml. Significant correlations were noted between the cortisol plasma concentration at 12 hours and methylprednisolone clearance and area under the concentration versus time curve (AUC). Interpatient variability in the disposition of methylprednisolone and cortisol response noted during the early post-transplant period contradict the clinical assumptions which underlie the fixed dosing protocols currently utilized for methylprednisolone.     

Pulmonary function in the early postoperative period

To the author's knowledge, an intensive investigation of pulmonary function during the first 2 postoperative days has not previously been reported. Consequently, in this study the effect of regional surgery on respiratory function, monitored every 4 h during the first 2 postoperative days, was analyzed. Hypoxaemia was a constant finding in all patients undergoing general anaesthesia. The degree and duration of hypoxaemia and spirometry changes were related to the site of surgical incision. Clinical signs of atelectasis were commonly observed during the first postoperative day and occurred after the change in PO2 and spirometry. Atelectasis was more common in patients having upper abdominal surgery. The current investigation reveals that the earliest postoperative change indicative of atelectasis is the fall in PO2; that auscultatory changes do not always occur in the presence of postoperative hypoxaemia; that auscultatory signs are not indicative of the extent of the PO2 fall; and that radiology represents a crude method of assessing postoperative atelectasis.     

The problem of acute pain in postoperative period]

The problem of postoperative pain remains actual despite the existence of a variety of pharmaceutical and nonpharmaceutical methods of anesthesia. Acute postoperative pain is an essential component of the surgical stress syndrome. Opioid analgetics (Buprenorfin, Nubain, Tramal, Promedol, Morphine) take the leading position among other types of analgetics. Present-day individual approach to administration of analgetics is still imperfect. The use of a standard dose of analgetics appears to be inadequate in a number of patients. The increase of opioids dose may lead to adverse reactions. In view of this it is valid to use nonsteroid antinflammatory medicines (Ketorolac). The choice of a proper dose of an analgetic is critically important in achieving adequate anesthesia. Patient-controlled analgesia (PCA) or "analgesia on demand" is an alternative to administration of analgetics. The major advantage of PCA is the opportunity to achieve the rate of analgesia, according to individual demand of a patient. Besides, PCA allows to reach the desired effect much faster and to maintain the stable plasma level of an analgetic. 2-year experience of the PCA use in more than 200 patients of the National Research Centre for Surgery ICU has been analysed. The authors advocate use of PCA in clinical practice.     

Interventricular communication in the neonatal period]

Fe(II)-tetrakis-N,N,N',N'(2-pyridylmethyl) ethylenediamine (Fe-TPEN) catalyzes the dismutation of superoxide, and blocks the toxic effect of paraquat on Escherichia coli growth and survival. We examined antioxidative effects of Fe-TPEN on lipid peroxidation and t-butyl hydroperoxide induced cell damage. Fe-TPEN inhibited the FeSO4/H2O2 induced lipid peroxidation in the rat liver homogenates with an IC50 value of 30.2 microM, and protected Ac2F cell damage by t-butyl hydroperoxide in a dose-dependent manner (EC50 value is 2.6 microM). Also, hepatoprotective effect of Fe-TPEN (5 mg/kg, i.p.) was investigated using CCl4 induced liver injury in rats. This complex inhibited the elevation of serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels in CCl4 induced liver injuries, and improved submassive necrosis and fatty degeneration of the hepatocytes. Fe-TPEN also prevented the loss of total and nonprotein SH contents, glutathione peroxidase and glutathione-S-transferase activity in cytosol of rat liver. Although the exact mechanism of action is not clear, antioxidative properties as well as attenuation of hepatocellular defense systems by Fe-TPEN seem to be important on its potent hepatoprotective effect in CCl4-intoxicated rat.     

Prevalence of gallstones in the neonatal period]

The prevalence of infection with Mycobacterium avium complex (MAC) has increased since the outbreak of the HIV pandemic. This complex comprises two organisms: M. avium (mostly) and M. intracellulare (rarely). The source of MAC infection is not known. The principal risk factors for disseminated MAC infection in a patient with HIV infection are a low CD4 count and a previous opportunistic infection. The symptoms of disseminated MAC infection resemble those of HIV wasting; a positive culture of normally sterile tissue confirms a MAC infection. There is reserve with regard to routine prophylaxis in HIV-infected persons because of the possible development of resistance, interaction with other drugs used in AIDS, toxicity and possible absorption disorders which might cause prophylaxis to fail. For the treatment of disseminated MAC infection, a combination of at least two medicaments (macrolides and ethambutol) is recommended.     

Significance of arterial ketone body ratio as a parameter of oxygen metabolism in cardiac surgery]

Postoperative course after cardiac surgery is characterized by a progressive increased cellular oxygen demand and limited oxygen supply. It is mandatory to assess the adequacy of tissue oxygenation and to correct inadequate oxygenation rapidly in cardiac surgery. The present study was designed to evaluate the relationship between the arterial ketone body ratio (AKBR) and the status of oxygen demand and supply relationship in cardiac surgery. We measured oxygen consumption, oxygen delivery, oxygen extraction, mixed venous oxygen saturation, lactate, lactate/pyruvate (L/P) and AKBR in 43 patients undergoing open heart surgery at selected 10 periods before, during and after cardiopulmonary bypass (CPB). AKBR significantly decreased immediately after the beginning of CPB and returned to pre-CPB level more quickly than lactate and L/P did. AKBR at several periods a significant correlation with lactate and L/P at delayed periods. There was a significant correlation between AKBR and L/P during and after CPB. Furthermore, oxygen consumption, oxygen extraction, mixed venous oxygen saturation, and lactate were correlated with AKBR significantly. But there was no correlation between the parameter of oxygen metabolism and both lactate and L/P. In conclusion, it appears from these data that AKBR in cardiac surgery may be helpful as a rapid guide for estimating the degree of anaerobiosis.     

The dynamics of the tissue oxygen regimen in patients with circulatory encephalopathy under the influence of oxygen baths]

AIM: To compare the proposed diagnostic criteria of subacute infectious endocarditis (SIE) to criteria developed by von Reyn et al. and by Duke Endocarditis Service. MATERIALS AND METHODS: 69 SIE cases and suspected recurrences have been analysed for patients observed in the Therapeutic Clinic of the Moscow medical University in 1990-1997. RESULTS: According to the authors' criteria accurate and tentative SIE diagnosis were made in 82 and 18% of patients, respectively. The other two diagnostic approaches in this situation increase the percentage of presumptive diagnosis and decrease that of the definite one. CONCLUSION: The criteria proposed by the authors are more sensitive in diagnosis of definite SIE, are less dependent on echocardiography quality and bacteriological diagnosis.     

Gait pattern in the early recovery period after stroke

The gait patterns of eighteen patients who had had a single infarct due to obstruction of the middle cerebral artery were evaluated within one week after the patients had resumed independent walking and before a gait rehabilitation program had been initiated. Gait was analyzed with use of motion analysis, force-plate recordings, and dynamic surface electromyographic studies of the muscles of the lower extremities. The patterns of motion of the lower extremity on the hemiplegic side had a stronger association with the clinical severity of muscle weakness than with the degree of spasticity, balance control, or phasic muscle activity. There was a delay in the initiation of flexion of the hip during the pre-swing phase, and flexion of the hip and knee as well as dorsiflexion of the ankle progressed only slightly during the swing phase. During the stance phase, there was decreased extension of the hip that was related to decreased muscle effort and a coupling between flexion of the knee and dorsiflexion of the ankle. The abnormal patterns of motion altered the velocity, the length of the stride, the cadence, and all phases of the gait cycle. The duration of the pre-swing phase was prolonged for the patients who had the slowest gait velocities. There also were abnormal movements of the upper extremity, the trunk, the pelvis, and the lower extremity on the unaffected side in an effort to compensate for the decreased velocity on the hemiplegic side. As velocity improved, these abnormal movements decreased. Therefore, the goal of therapy should be to improve muscle strength and coordination on the hemiplegic side, especially during the pre-swing phase.     

Ozone therapy of diffuse peritonitis in the early postoperative period

The functional status of the oxidative-antioxidative system was studied in 72 patients after vast cancer operations. Traditional surgical treatment and its combination with intraoperative irradiation were shown to lead to tense antioxidative defense and to suppressed T-cell immunity and to call for antioxidative and immunomodulating therapy. High intraoperative blood loss complicated by hemorrhagic shock injured the oxidative-antioxidative system greatly. The magnitude of this damage correlated with the rate of prehypoxia. Addition of the potent antioxidant Ceruloplasmin to the drug regimen normalized a recovery period, helped to correct posthypoxic multiorgan insufficiency, to recover oxidative-antioxidative balance, and to decrease the incidence of pyoinflammatory complications. Patients with endogenous intoxication showed activated lipid peroxidation, decreased functional activity of antioxidative defense components and of T-cell immunity in homeostasis. The use of Ceruloplasmin and Laprot had pronounced antiinflammatory and detoxifying effects on the patient's body and activated its antioxidative defense.     

The prognosis of the severity of the early postop period in patients operated for gastrointestinal bleeding

The oxygen metabolism was studied up in patients, operated on for gastrointestinal haemorrhage after conduction of an urgent measures for hypovolemia elimination. While favourable course of an early postoperative period the systoles rate (SR) was less than 116 in a minute. Sensitivity of the symptom (frequency of the symptom revealed in the patients of this group) was 94.54%, specificity (the absence of the symptom in the patients of other groups)--53.31%. Constant tachycardia (SR more than 116 in a minute) is a prognostic symptom of exitus lethalis. Its sensitivity is 100%, specificity--83.14%. Moderate loss of xi-potential of erythrocytes is complementary symptom, permitting exitus lethalis prognostication conduction. The increase of ratio of lactic acid and piruvate contents in the blood up to more than 5.25 conventional units is characteristically for the complicated but favourable for life an early postoperative course. Sensitivity of the feature is 91.17%, specificity--60.29%.     

The effect of selenium supplementation during the early post-mating period on embryonic survival in sheep

The functioning of the guinea-pig isolated portal vein was monitored by measuring spontaneous mechanical activity, responses to electrical stimulation and administered noradrenaline in normoxic conditions. The effect of hypoxia, induced by bubbling the physiological bathing solution with a 95% N(2)/5% CO(2) gas mixture, on the mechanical performance of the vein was then assessed. Spontaneous activity declined in hypoxia, with mean contraction tension reduced by 55 + or - 8.8%. The responses to electrical field stimulation (2-32 Hz, 0.7 msec. 70 V) were lowered by 14 + or - 4.6% but contractions produced by a range of noradrenaline concentrations (0.01-160 mu M) were unaffected by hypoxia. Substitution of glucose in the bathing solution with sucrose, a substrate unavailable to the cells for energy generation, produced a marked enhancement of the effect of hypoxia. Spontaneous activity was reduced by 76 + or - 8.3%, electrically-induced activity by 80 + or - 14.4% and noradrenaline-induced responses by 85 + or - 6.8%. Although in normoxia the activity and responses of the portal vein were unaffected by the presence of alpha-tocopherol, it significantly protected the functioning of the vein in hypoxic conditions. This effect was concentration-dependent within the range 10-160 mu M and was most marked when glucose was replaced by sucrose in the bathing solution.     

The early development of sex-differentiated patterns of social influence.

Examined the verbal social influence styles of 36 boys and girls aged 41–52 mo and 38 boys and girls aged 54–66 mo. Ss were observed in the classroom for 36 min each, over several months. Results indicate that boys emitted a greater number of influence attempts than girls and that this was almost entirely due to their greater use of direct forms of requests. This sex-differentiation in the use of direct requests became more pronounced with age. In contrast, girls increased their use of indirect forms of influence between the ages of 3 and 5 yrs. Success of peer influence attempts towards boys decreased with age from 3 to 5 yrs, especially attempts of the indirect type, while success of attempts toward girls remained relatively stable with age. Girls' direct requests were more successful toward same-sex than opposite-sex peers. These patterns are discussed in terms of the role they might play in perpetuating the rigidity with which children establish same-sex groups during the preschool period. (French abstract) (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)