A prospective controlled trial of cold-storage versus machine-perfusion preservation in cadaveric renal transplantation

A prospective controlled study was carried out in 60 consecutive cadaver renal donors comparing cold storage to pulsatile machine-perfusion preservation. Each donor served as its own control, by allocating one of the kidneys to each of the two preservation methods. There were 51 evaluable pairs of kidneys. Recipient age, panel-reactive antibody level, history of prior renal transplant, and immunosuppressive regimen were similar in the two preservation groups. Almost all recipients were treated with cyclosporine, and over 50% received antilymphoblast globulin. Total cold ischemic time was 1262 +/- 387 min in the machine-perfused group and 1309 +/- 426 min in the cold-storage group (P = NS). Prolonged ischemia (greater than 24 hr) occurred in 31% of machine-perfused and 22% of cold-stored kidneys (P = NS). Post-operative serum creatinine levels at 1, 7, and 30 days posttransplant were similar in both groups. Dialysis requirements were also similar, with 21 recipients of machine-perfused kidneys (41%) requiring at least one dialysis treatment compared to 16 patients (31%) in the cold-stored group (P = NS); the mean number of dialysis treatments required was 3.14 +/- 1.46 and 3.06 +/- 1.29, respectively (P = NS). Long ischemic time (greater than 24 hr) was associated with a higher rate of dialysis requirement in both groups, but in neither case did this achieve statistical significance. The distribution of graft losses within the first 30 days was similar in both groups, and the incidence of preservation-related graft failure was not significantly different. These results demonstrate that, in the cyclosporine era, machine perfusion offers no significant advantages over cold storage for cadaver renal preservation. Because machine perfusion is considerably more expensive and cold storage is simpler and facilitates the logistics of organ sharing, we recommend simple hypothermic storage of renal allografts as the preservation method of choice.     

Changes in heart rate and rhythm after intramuscular succinylcholine with or without atropine in anesthetized children

The effects of intramuscular injections of succinylcholine with or without atropine on heart rate and rhythm were studied in 50 unpremedicated children 6-18 months of age. All had anesthesia induced with N2O-O2 and halothane 2% by face mask. Sixty seconds later, one of four study drugs or drug combinations was injected into the deltoid muscle of patients in groups 1-4. Following injection, halothane concentration was reduced to 1%, and ventilation was controlled. Patients given atropine only (0.02 mg/kg), succinylcholine only (4 mg/kg), or a combination of both (4 mg/kg succinylcholine plus 0.02 mg/kg atropine) showed transient increases in heart rate to 106 +/- 7.5%, 113 +/- 11.8%, and 109 +/- 10.1% (mean +/- SD) of control, followed by a decrease to 78 +/- 6.7%, 79 +/- 9.4%, and 80 +/- 10.5%, respectively, in 2-3 min after injection. Patients given a combination of succinylcholine (4 mg/kg) plus a higher dose of atropine (0.03 mg/kg) also had a transient increase in heart rate to 107 +/- 7.5%, followed by a decrease to 82 +/- 11.8% 2 min after injection. However, this group differed from the other three groups in presenting a second, prolonged increase in heart rate to 115 +/- 9.0% of preinjection levels. Patients in group 5 (controls) received no injections. Their heart rate decreased to 76 +/- 10.78% of preinduction level within 90 sec of induction, and remained unchanged thereafter. We conclude that succinylcholine (4 mg/kg) can be used intramuscularly with or without atropine (0.02 mg/kg) in lightly anesthetized young children without producing severe bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blockade of LTB4-induced chemotaxis by bioactive molecules interfering with the BLT2-Gαi interaction

BLT2, a low-affinity leukotriene B₄ (LTB₄) receptor, is a member of the G-protein coupled receptor (GPCR) family and is involved in the pathogenesis of inflammatory diseases such as asthma. Despite its clinical implications, however, no pharmacological inhibitors are available. In the present study, we screened for small molecules that interfere with the interaction between the third intracellular loop region of BLT2 (BLT2_iL3) and the Gα_i3 protein subunit (Gα_i3), using a high-throughput screening (HTS) assay with a library of 1040 FDA-approved drugs and bioactive compounds. We identified two small molecules—purpurin [1,2,4-trihydroxy-9,10-anthraquinone; IC₅₀ = 1.6 μM for BLT2] and chloranil [tetrachloro-1,4-benzoquinone; IC₅₀ = 0.42 μM for BLT2]—as specific BLT2-blocking agents. We found that blockade of the BLT2_iL3-Gα_i3 interaction by these small molecules inhibited the BLT2-downstream signaling cascade. For example, BLT2-signaling to phosphoinositide-3 kinase (PI3K)/Akt phosphorylation was completely abolished by these molecules. Furthermore, we observed that these small molecules blocked LTB₄-induced chemotaxis by inhibiting the BLT2-PI3K/Akt-downstream, Rac1-reactive oxygen species-dependent pathway. Taken together, our results show that purpurin and chloranil interfere with the interaction between BLT2_iL3 and Gα_i3 and thus block the biological functions of BLT2 (e.g., chemotaxis). The present findings suggest a potential application of purpurin and chloranil as pharmacological therapeutic agents against BLT2-associated inflammatory human diseases.     

Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial.

OBJECTIVE: This pilot study's aim was to establish feasibility of a protocol for delayed cord clamping (DCC) versus immediate cord clamping (ICC) at preterm birth and to examine its effects on initial blood pressure and other outcomes. STUDY DESIGN: A randomized controlled trial recruited 32 infants between 24 and 32 weeks. Immediately before delivery, mothers were randomized to ICC (cord clamped at 5 to 10 seconds) or DCC (30- to 45-second delay in cord clamping) groups. RESULTS: Intention-to-treat analyses revealed that the DCC group were more likely to have higher initial mean blood pressures (adjusted OR 3.4) and less likely to be discharged on oxygen (adjusted OR 8.6). DCC group infants had higher initial glucose levels (ICC=36 mg/dl, DCC=73.1 mg/dl; p=0.02). CONCLUSION: The research design is feasible. The immediate benefit of improved blood pressure was confirmed and other findings deserve consideration for further study.     

Excitation of rat hippocampal interneurons via modulation of endogenous agonist activity at the α7 nicotinic ACh receptor

The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR) is prominently expressed in the hippocampus where it is thought to play a role in the regulation of cognitive function. In this study, we have investigated the effects of 5-hydroxyindole (5-HI), a positive modulator of the α7 nAChR, on GABAergic activity in hippocampal CA1 stratum radiatum interneurons in acute rat brain slices. Superfusion of 5-HI (100 μ m ) increased the mean frequency and amplitude of spontaneous IPSCs (sIPSCs). The potentiation was occluded by pretreatment of slices with: (1) a high concentration of the broad-spectrum agonist nicotine to desensitize the α7 receptor, (2) an α7 nAChR antagonist, and (3) tetrodotoxin to block action potential firing. These results indicate that facilitation by 5-HI was mediated by the α7 nAChR and required neuronal excitation. In contrast, 5-HI had no effect on sIPSCs recorded in hippocampal slices from younger animals, even though the expression of functional α7 nAChRs was confirmed by agonist application experiments. In these slices, 5-HI only enhanced sIPSCs after pretreatment with the acetylcholinesterase inhibitor Bw284c51. Taken together, our results suggest that 5-HI facilitates GABAergic transmission via excitation of the α7 nAChR, and that this effect requires the presence of the endogenous agonist ACh in the extracellular environment of the receptor.     

The effect of skin surface warming during anesthesia preparation on preventing redistribution hypothermia in the early operative period of off-pump coronary artery bypass surgery.

OBJECTIVE: Redistribution hypothermia adversely affects hemodynamics and postoperative recovery in patients undergoing cardiac surgery. In off-pump coronary bypass surgery (OPCAB), maintaining the temperature is important because warming by cardiopulmonary bypass is omitted. Pre-warming studies reported earlier showing pre-warming as an effective means of preventing redistribution hypothermia was time consuming since it required at least 1-2h to pre-warm the patients before the surgery. Because pre-warming for such a long time is impractical in clinical practice, this study evaluated the efficacy of active warming during the preanesthetic period for the prevention of redistribution hypothermia in the early operative period of OPCAB. METHODS: After gaining the approval of Institutional Review Board and informed consent from the patients, 40 patients undergoing OPCAB were divided into control and pre-warming groups. The patients in control group (n=20) were managed with warm mattresses and cotton blankets, whereas patients in pre-warming group (n=20) were actively warmed with a forced-air warming device before the induction of anesthesia. Hemodynamic variables and temperature were recorded before anesthesia (Tpre) and at 30 min intervals after anesthesia for 90 min (T30, T60, and T90). RESULTS: Active warming duration was 49.7+/-9.9 min. There were no statistically significant differences in skin temperature, core temperature and hemodynamic variables between the two groups at preinduction period except for mean arterial pressure and central venous pressure. The core temperature at T30, T60, and T90 was statistically higher in pre-warming group than that in control group. Core temperature of six (30%) and seven patients (35%) in control group was reduced below 35 degrees C at T60 and T90, respectively, whereas core temperature of only one patient (5%) in pre-warming group was reduced below 35 degrees C at T90 (P=0.02). CONCLUSIONS: Active warming using forced air blanket before the induction of anesthesia reduced the incidence and degree of redistribution hypothermia in patients undergoing OPCAB. It is a simple method with reasonable cost, which does not delay the induction of anesthesia nor the surgery.     

Diagnostic value of the radioisotope erection penogram for vasculogenic impotence

Radioisotope erection penography of 113 consecutive impotent patients (41 with psychogenic and 72 with vasculogenic impotence) and 15 normal potent men were obtained. Twenty minutes after intracavernous injection of 99mtechnetium-pertechnetate 40 mg. papaverine hydrochloride were administered into the corpus cavernosum to induce erection. A gamma camera with a pinhole collimator was used to monitor the radioactivity. Various penogram indexes were calculated from the time activity curve and their usefulness was evaluated. Index A1 was useful to differentiate vasculogenic and psychogenic importance. Indexes V1 and V2 were useful to differentiate arteriogenic and venogenic impotence. The radioisotope erection penogram is a simple, less invasive and valuable screening test in the identification of vasculogenic impotence, and is effective in differentiating arteriogenic and venogenic impotence.