Liver Transplantation Across Rh Blood Group Barriers Increases the Risk of Biliary Complications

Background Cold ischemia time and the presence of postoperative hepatic arterial thrombosis have been associated with biliary complications (BC) after liver transplantation. An ABO-incompatible blood group has also been suggested as a factor for predisposal towards BC. However, the influence of Rh nonidentity has not been studied previously. Materials Three hundred fifty six liver transplants were performed from 1995 to 2000 at our hospital. BC incidence and risk factors were studied in 345 patients. Results Seventy patients (20%) presented BC after liver transplantation. Bile leakage (24/45%) and stenotic anastomosis (21/30%) were the most frequent complications. Presence of BC in Rh-nonidentical graft–host cases (23/76, 30%) was higher than in Rh-identical grafts (47/269, 17%) (P = 0.01). BC was also more frequent in grafts with arterial thrombosis (9/25, 36% vs 60/319, 19%; P = 0.03) and grafts with cold ischemia time longer than 430 min (26/174, 15% vs 44/171, 26%; P = 0.01). Multivariate logistic regression confirmed that Rh graft–host nonidentical blood groups [RR = 2(1.1–3.6); P = 0.02], arterial thrombosis [RR = 2.6(1.1–6.4); P = 0.02] and cold ischemia time longer than 430 min [RR = 1.8(1–3.2); P = 0.02] were risk factors for presenting BC. Conclusion Liver transplantation using Rh graft–host nonidentical blood groups leads to a greater incidence of BC.     

Sulphhydryl-modifying Reagents Alter Ototoxin Block of Muscarinic Receptor-linked Phosphoinositide Turnover in the Cochlea

In the 12-day-old rat cochlea, the synthesis of inositol phosphates (IPs) can be activated via M3 cholinoceptors. This stimulation is blocked by ototoxins (mercury, ethacrynate, cisplatin, neomycin), drugs with side effects that lead to damage of hair cells and strial cells. As these toxic effects can be reversed in vivo by thiol molecules, we investigated whether modifications of thiol compounds could be involved in ototoxin-induced inhibition of the IP turnover in the cochlea. For this purpose, we assessed whether the sulphhydryl-modifying reagents N -ethylmaleimide and cadmium modify the carbachol-stimulated formation of IPs in the 12-day-old rat cochlea. Both molecules inhibit the carbachol effect on a dose-dependent way without altering the basal metabolism of IPs. As cadmium may block some calcium channels, the effect of verapamil, another calcium channel antagonist, was tested. Verapamil (1 –50 μM) does not alter carbachol-evoked IP formation, suggesting that the inhibitory effect of cadmium is not due to a calcium influx block. Binding experiments with the muscarinic ligand quinuclidinyl benzylate (QNB) showed that the sulphhydryl-modifying reagents do not displace QNB from binding sites. Combining ototoxins and reagents shows that N -ethylmaleimide acts synergistically with all ototoxins but ethacrynate while cadmium does so only with mercury. Both N -ethylmaleimide and cadmium have additive effects with ethacrynate. As a supplement, disulphide bond-modifying agents do not alter the carbachol-enhanced metabolism of IPs. These results suggest that molecules having thiol-modifying properties inhibit the carbachol-induced turnover of IPs without acting at the muscarinic sites. Since thiol modifiers and ethacrynate share similar features in both QNB binding and IP response it is hypothesized that they strike common targets, possibly G proteins.     

Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.     

Regulation of glucose homeostasis in pre-obese Zucker rats before and after weaning

This study was undertaken to determine the changes which could occur in glucose homeostatis during the suckling-weaning transition in the genetically obese Zucker (fa/fa) rat. Glucose kinetics and glucose utilization in individual tissues were determined in 15-day-old suckling and 30-day-old weaned obese Zucker rats either in the post-absorptive state or during a glucose infusion. During suckling, glucose turnover rates in the basal state as well as glucose production and utilization during the glucose infusion were identical in lean and obese rats. Furthermore, individual tissue glucose utilizations were similar in the two groups of rats, except in brown adipose tissue where utilization was lower in obese than in lean rats during the glucose challenge. After weaning, glucose turnover rates and glucose utilization in individual tissues were identical in the two genotypes in the basal state. During the glucose infusion, hepatic glucose production was less suppressed in the obese. Furthermore, glucose utilization was significantly lower in muscles (extensor digitorum longus, tibialis anterior, diaphragm) and higher in white adipose tissue of obese rats. These data show that, before weaning, pre-obese Zucker rats present a perturbation only in the uptake of glucose in brown adipose tissue. Major defects in the regulation of glucose homeostatis occur after weaning.     

Cervical pregnancy complicated with group B streptococcal meningitis.

Maternal group B streptococcal infection is an uncommon entity. Herein we describe a case of a 27-year-old-woman who presented life-threateniing group B streptococcus meningitis with an ectopic cervical pregnancy. No other infectious focus have been found. To our knowledge this is the first time that this association has been reported.     

Niflumic acid-induced increase in potassium currents in frog motor nerve terminals: effects on transmitter release

The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied on frog neuromuscular preparations by conventional electrophysiological techniques. Niflumic acid reduced the amplitude and increased the latency of endplate potentials in a concentration-dependent manner. Neuromuscular junctions pretreated with niflumic acid (0.05–0.5 mM) showed much less depression than control when they were stimulated with trains of impulses. Inhibition of acetylcholine release was reverted by raising the extracellular Ca²⁺ concentration but not by simply washing out the preparations with niflumic acid-free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal antiinflamatory drug, did not affect the niflumic acid-induced inhibition of evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of miniature endplate potentials and had a dual action on the frequency of miniatures: it decreased their frequency at 0.1 mM whereas it produced an enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid (0.1–1 mM) reversibly increased the amplitude and affected the kinetics of presynaptic voltage-activated K⁺ current and Ca²⁺-activated K⁺ current in a concentration-dependent manner. Niflumic acid (0.1–1 mM) irreversibly decreased the amplitude and reversibly affected the kinetics of the nodal Na⁺ current. Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion, niflumic acid reduces acetylcholine release by increasing presynaptic K⁺ currents. This may shorten the depolarizing phase of the presynaptic action potential and may reduce the entry of Ca²⁺ with each impulse.