Anti-D in a D-positive renal transplant patient

PURPOSE: We report a case of postoperative reparalysis in the recovery room, following nebulized epinephrine. The patient was pharmacologically reversed with edrophonium after paralysis with rocuronium. CLINICAL FINDINGS: A 12-yr-old girl developed postoperative reparalysis following the intraoperative administration of rocuronium. A total of 0.92 mg.kg-1 rocuronium was administered. After surgery, pharmacological reversal was achieved with 20 mg edrophonium with 0.15 mg atropine sulfate iv 35 min after the last administration of rocuronium. Muscular relaxation was monitored using an ulnar peripheral nerve stimulator (PNS). After reversal, a full train-of-four and sustained tetanus at 50 Hz were present. In the recovery room, following nebulized epinephrine, the patient became apneic. The patient was paralyzed and an ulnar PNS demonstrated only one faint twitch. The paralysis was reversed with 1.5 mg neostigmine with 0.3 mg glycopyrrolate. CONCLUSION: Postoperative reparalysis following rocuronium may be a cause of postoperative respiratory distress. The definitive diagnosis is made using PNS and observing the response to pharmacological reversal. Nebulized epinephrine may have a previously undescribed role in the development of postoperative reparalysis.     

The pharmacokinetics and pharmacodynamics of the oral iron chelator deferiprone (L1) in relation to hemoglobin levels

Recently, we demonstrated that administration of the orally active iron chelating agent deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one (L1)) at 6-hour intervals results in significantly greater urinary iron excretion than that induced during administration of the drug at 12-hour intervals. That study was conducted in thalassemia patients, all of whom had received a packed red cell transfusion of 15 cc/kg. 72 hours prior to evaluation of urinary iron excretion, at a time when endogenous erythropoiesis would be expected to be at its lowest. In clinical practice however, thalassemia patients, suppression of endogenous erythropoiesis is not sustained between transfusions. We set out to determine the influence that administration of deferiprone has on urinary iron excretion at lower hemoglobin concentrations, immediately prior to transfusion. We hypothesized that hemoglobin levels will affect the ability of deferiprone to chelate iron. Ten regularly transfused patients with homozygous beta-thalassemia (HBT) aged mean +/- SD, 20.9 +/- 4.7, range 13 - 27 years, receiving long-term therapy with deferiprone, were treated with deferiprone 75 mg/kg/day, administered every 6 hours (or every 12 hours) for 72 hours immediately prior to a blood transfusion in the first month. One month later each patient received the other of the 2 dosing regimens for 72 hours immediately prior to transfusion. The deferiprone-induced 24-hour urinary iron excretion was similar during both dosing regimens; 0.56 +/- 0.45 mg/kg when L1 was given every 6 hours and 0.48 +/- 0.52 mg/kg when L1 was administered every 12 hours (p = 0.79). However, the calculated 24-hour area under the plasma concentration-time curve (AUC0-24) of deferiprone was significantly lower when deferiprone was administered at 6-hour intervals (6,762.8 +/- 1,601.6 mg*min/l), than that observed when deferiprone was administered every 12 hours (8,250.1 +/- 1,235.7 mg*min/l) (p = 0.04). The pharmacokinetics of deferiprone when administered immediately prior to transfusions are different from those following transfusions. More studies assessing total body iron excretion are needed to determine the contribution of the fecal route in iron excretion.     

The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults

OBJECTIVE: Growth hormone (GH) replacement therapy in hypopituitary adults is associated with sodium and water retention. The underlying mechanisms are incompletely understood and a possible contribution of altered cortisol metabolism or action has not been evaluated. We have investigated the effect of GH replacement therapy on cortisol metabolism, cortisol binding globulin and in-vitro glucocorticoid sensitivity in a group of adult hypopituitary patients. DESIGN AND PATIENTS: We studied 19 adult hypopituitary patients (18 adult onset, M:F, 6:13), who were receiving conventional hydrocortisone (16 patients), thyroxine (14 patients), triiodothyronine (1 patient), sex steroid (9 patients), human chorionic gonadotrophin (1 patient) or desmopressin (6 patients) replacement during a 6-month, double blind controlled trial of GH therapy (active:placebo, 8:11) followed by a 6-month open phase of GH (mean dose: 0.2 IU/kg/week, range 0.051-0.27) and after a 6-week washout phase following discontinuation of GH therapy. MEASUREMENTS: Twenty-four-hour urine free cortisol, cortisol metabolites (CoM), ratio 11-hydroxy/11-oxo CoM (F/E) and ratio 5 alpha/beta tetrahydrocortisol were measured at 6 months, 12 months and after the 6 week washout phase. Serum cortisol binding globulin was measured basally, at 6 months, 12 months and after washout. Glucocorticoid sensitivity was determined in lymphocyte preparations from 8 patients, during GH therapy and after washout, using an in-vitro technique dependent on dexamethasone suppression of phytohaemagglutinin-stimulated thymidine incorporation into DNA. Plasma renin activity and aldosterone were measured after 6-12 months GH therapy and after washout. RESULTS: After 6 months of GH, in patients on hydrocortisone (n = 9), there were significant decreases in CoM (mean decrement 21%, P < 0.01), F/E (mean decreased from 1.27 to 1.0, P = 0.04; reference range 0.33-1.29) and 5 alpha/5 beta tetrahydrocortisol (mean decreased from 0.67 to 0.48, P = 0.01) and a subsequent increase after washout. Patients not on hydrocortisone (n = 2) demonstrated a normal basal F/E falling by 25% on GH therapy but no change in CoM. During 12 months of GH therapy, patients on hydrocortisone (n = 7) demonstrated a further trend to decrement in CoM (P = 0.09) which reversed after washout (P = 0.04). Urine free cortisol tended to fall during GH therapy and increased significantly following washout after 12 months treatment (P < 0.02). Serum cortisol binding globulin decreased by 20% (P < 0.05) during 12 months GH treatment but remained within the reference range. In-vitro studies demonstrated a trend to reduced glucocorticoid sensitivity on GH therapy; the maximum inhibition of phytohaemagglutinin by dexamethasone tended to be less on GH therapy (P = 0.052) and was also lower than in 29 normal volunteers (P < 0.05). There were no significant changes in plasma renin but there was a small increment in aldosterone in recumbent patients (P = 0.04) during the open phase of GH therapy in the placebo arm. CONCLUSIONS: GH therapy in hypopituitary adults is associated with an apparent reduction in availability of administered hydrocortisone as measured by urine cortisol metabolites and urine free cortisol. This effect is unlikely to be clinically significant except possibly in ACTH deficient subjects on suboptimal hydrocortisone replacement. The changes in F/E suggest that GH may directly or indirectly modulate the activity of 11 beta-hydroxysteroid dehydrogenase. The apparent decrease in glucocorticoid sensitivity during GH therapy, demonstrated in vitro, merits further investigation.     

Risk factors for high blood lead levels among the general population in Taiwan

BACKGROUND: Tacrolimus (FK506) may represent a major advance in the management of allograft rejection after solid organ transplantation. In August 1994 a European heart transplantation pilot study was initiated to assess the efficacy and safety of tacrolimus when administered exclusively through an oral route. METHODS: Eighty-two heart transplant recipients were randomized to treatment (2:1 ratio) with either tacrolimus- (n=54) or cyclosporine-based therapy (n=28). RESULTS: No significant differences were evident between the two treatment groups in either rejection or survival rates at 1 year. Kaplan-Meier estimates of the freedom from rejection were 26.3% and 18.5%, respectively, for the tacrolimus and cyclosporine treatment groups (p=.444). Survival rates were 79.6% and 92.9% (p=.125). At 3 of the 5 centers, patients received antithymocyte globulin during the immediate postoperative period and fared better than those who did not (with acute rejection-free rates of 49.2% and 26.7% for tacrolimus and cyclosporine, respectively [p=.080], as opposed to 7.1% and 8.3% [p=.965]; patient survival rates of 84.6% and 93.3% [p=.382] vs 75.0% and 92.3% [p=.243]). The overall rates of infection, impaired renal function (31.5% vs 21.4%), and glucose intolerance (7.0% vs 4.3%) did not differ significantly between the tacrolimus and cyclosporine treatment groups. Tacrolimus seemed to possess an advantage with regard to a reduced requirement for antihypertensive therapy (59.5% vs 87.5%, p=.025). CONCLUSIONS: Immunosuppression with oral tacrolimus provides a viable alternative to treatment with cyclosporine, particularly when administered in conjunction with antibody therapy. Further studies are warranted to optimize the administration of tacrolimus in this indication.     

Status of cerebral circulation in patients with hemiplegia of vascular and traumatic origin treated with decimeter therapy and an alternating magnetic field

Results of treating 181 patients for hemiparesis after a cerebral stroke or a craniocerebral injury by local exposure of the pathological focus to decimeter electromagnetic waves (DW) and alternating magnetic field (AMF) are presented. It is shown that these treatment methods improve the cerebral circulation and contribute to earlier restoration of the motor functions, especially, if used in combination with sulfide baths, therapeutic physical exercises and massage. The therapeutic effectiveness of the DW- and AMF-therapy is confirmed objectively by so informative examination methods, as rheoencephalography, ultrasonic dopplerography, and thermography.