Partial splenectomy in Gaucher's disease

In 11 children with hypersplenism due to Gaucher's disease, partial splenectomy was planned with the aim to prevent the development of postsplenectomy sepsis and also to slow the advance of the disease in the rest of the reticuloendothelial system by permitting continuing accumulation of the beta-glucocerebroside in the remaining splenic tissue. In seven children, partial splenectomy was performed successfully, the weight of the splenic tissue removed ranging from 400 to 3,680 g. The postoperative course was uneventful and the average duration of hospitalization was 12 days. In subsequent follow-up, isotope scanning demonstrated continuing growth of the splenic remnant and there were no episodes of postsplenectomy sepsis nor evidence of increased accumulation of beta-glucocerebroside in the liver or bones. These children showed a marked improvement in the growth curve and dramatic improvement in the hematologic picture. Of the four remaining children, in two, partial splenectomy was followed by complete removal of the remaining spleen due to necrosis, whereas in two, total splenectomy was performed since the huge spleens were extensively infarcted. Our experience suggests that partial splenectomy is the treatment of choice in the management of young patients with hypersplenism due to Gaucher's disease.     

Flow requirements for the Bain breathing circuit during anaesthesia for caesarean section

We studied the relationship between arterial carbon dioxide tension (PaCO2) and fresh gas flow (FGF) during use of the Bain breathing circuit for Caesarean section anaesthesia. Thirty-one patients undergoing Caesarean section were anaesthetised using the Bain circuit with intermittent positive pressure ventilation. The PaCO2 were measured at FGF of 70 ml X kg-1 X min-1, 80 ml X kg-1 X min-1, and 100 ml X kg-1 X min-1. The FGF requirement to maintain a given PaCO2 during Caesarean section anaesthesia is the same as the requirements for nonpregnant subjects, despite the increase in carbon dioxide production associated with pregnancy. This is probably because the total FGF determined by body weight and given during Caesarean section anaesthesia is 15-20 per cent higher than nonpregnant levels, due to the weight gain associated with pregnancy. A FGF of 100 ml X kg-1 of pregnant weight/min maintains PaCO2 of 4.44 kPa predelivery, which is in the desirable range of PaCO2 during Caesarean section.     

Pharmacokinetics and pharmacodynamics of epidural and intrathecal morphine

Spinal opiate analgesia has opened an exciting new field of research and has also rapidly gained widespread clinical acceptance. This mode of administration has obvious and definite advantages over conventional pain therapy; however, the field is still at an early stage of development. More research is clearly needed to provide methods for coping with some of the drawbacks of this method of pain relief. Important areas for future research include (1) the CSF kinetics of opiates; (2) the physiological mechanisms underlying the rostral spread of drugs within the CSF compartment; (3) a search for safer and more selective drugs; and (4) an evaluation of the extent to which pain-modulating systems at different levels in the CNS can be regulated by opiates and drugs interfering with other neurotransmitters. In this context it is essential to emphasize the importance of simultaneous study of the pharmacokinetics and the pharmacodynamic/clinical effects in providing a rational basis for a better understanding of the mechanisms of actions underlying spinal opiate analgesia.     

Computerized tomography diagnosis of diffuse intraperitoneal metastases after retroperitoneal lymphadenectomy for testicular carcinoma

We report 2 cases of diffuse intraperitoneal metastases from testicular carcinoma following transabdominal retroperitoneal lymphadenectomy. This is an unusual pattern of metastasis for nonseminomatous germ cell tumors and it is believed to be the result of direct seeding from lymphatic leakage secondary to surgery. The value of computerized tomography in diagnosing this entity is emphasized.     

Neuronal activity evoked by chronically implanted intracortical microelectrodes

The averaged evoked compound action potentials (AECAPs) were recorded from the ipsilateral pyramidal tract of awake, unrestrained cats before, during, and after continuous electrical stimulation of the cerebral cortex via chronically implanted activated iridium or platinum-30% iridium (Pt30%Ir) microelectrodes. After stimulating 24 h at 20 pulses per second (pps), using charge-balanced, 200-microseconds pulse pairs of 40 to 80 microA (400 to 800 microC/cm2, 8 to 16 nC/phase (ph), 2 to 4 A/cm2), there was a transient elevation of the threshold of the early (direct) and of the alte (transynaptic) components of the AECAP. After cessation of continuous stimulation at 80 microA, the threshold of the early component of the AECAP remained elevated for as long as 24 h and the late component as long as 4 days, indicating significant but reversible depression of the electrical excitability of cortical neurons close to the microelectrodes. In three cats stimulated 23 h/day for 1 week, the AECAP also recovered to their prestimulus threshold. In contrast, pulsing for 24 h at 320 microA (3200 microC/cm2, 64 nC/ph, 16 A/cm2) produced marked elevation of the threshold of the AECAPs which was not reversed by 7 to 12 days after termination of intracortical stimulation. The electrical excitability of neurons adjacent to (unpulsed) microelectrodes 2 mm from the pulsed electrode was not affected. The observations reported here, in conjunction with the histologic results reported in the companion paper, indicate that both the Pt30%Ir and the iridium microelectrodes can be operated safely at currents to at least 80 microA, charge/ph of 16 A/cm2, and a charge density of 800 microC/cm2 X ph. However, on the basis of the electrophysiologic criteria, both types appear to be unsafe when pulsed at 320 microA (64 nC/ph, 3200 microC/cm2 X ph, 16 A/cm2).     

Vitamin D3 derivatives inhibit the differentiation of Friend erythroleukemia cells

A number of vitamin D3 metabolites inhibit benzodiazepine- and dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells. The inhibition is dose dependent and occurs at nM concentrations. The order of potency of these compounds is 1,25-dihydroxycholecalciferol greater than 1,25,26-trihydroxycholecalciferol greater than 1,24R,25-trihydroxycholecalciferol greater than 1 alpha-hydroxycholecalciferol greater than 24R,25-dihydroxycholecalciferol greater than 25S,26-dihydroxycholecalciferol. The inhibition is maximal when the vitamin D3 analogs are added together with the inducer, and becomes progressively decreased with delayed addition. These results suggest that the vitamin D3 metabolites may play a regulatory role in erythropoiesis.     

Pharmacokinetics of intravenous bepridil in patients with coronary disease

The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing.