Transcutaneous bilirubin measurement in preterm infants]

Transcutaneous bilirubinometry is an effective screening tool for neonatal jaundice in full-term babies. But its accuracy is not shown yet in preterm infants. METHODOLOGY: We carried out a prospective study in a neonatal intensive care unit. The study included 47 preterm infants. From birth, a transcutaneous bilirubin measurement (BTc) using the BiliCheck was made on the forehead of each newborn every 8 h. Blood sampling for determination of total serum bilirubin (BS) was combined with BTc: 1) if value of BTc was higher than limits values for phototherapy; 2) on the second day of life and 3) 4 hours after cessation of phototherapy. RESULTS: Mean gestational age was 30 week and mean birth weight was 1419 g. We studied 151 pairs of BTc and BS. Mean values obtained by BTc and BS were respectively 160.6+/-50 mumol/L and 190.6+/-61.4 mumol/L. A significant correlation between BTc and BS was found. But the limits of agreement were very wide. The negative predictive value (NPV) of BTc was above 90% in each group of gestational age. DISCUSSION: The need for phototherapy cannot be determined by BTc in preterm infants. But the BTc is reliable when its value is under the limits for phototherapy. CONCLUSION: With a very high incidence of neonatal jaundice (87%) in our cohort, a value of BTc under the limits for phototherapy has a good NPV in preterm infants.     

25-Hydroxyvitamin D3 metabolism in a human leukemia cell line

Summary 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D₃ (25(OH)D₃) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD₃ to 1,25(OH)₂D₃ by HL-60, we exposed HL-60 cells to 25OHD₃ and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)₂D₃. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD₃ (19-Nor-25OHD₃). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD₃ also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)₂D₃ and similar to that of 25OHD₃. In agreement with the effect upon cell maturation, 19-Nor-25OHD₃ displaces³H-1,25(OH)₂D₃ from its HL-60 receptor with an efficiency comparable to 25OHD₃. Hence, HL-60 cells convert 25OHD₃ to 19-Nor-25OHD₃, and 19-Nor-25OHD₃ induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD₃.     

Radical cystectomy after coronary artery bypass graft

Nine patients have undergone single-stage radical cystectomy and ileal conduit urinary diversion two to fifty-one months after coronary artery bypass procedures. Two patients presenting with intractable angina at the time their malignant disease was being evaluated required bypass surgery before cystectomy could be undertaken. No significant cardiac morbidity occurred postoperatively, and all remain alive without evidence of malignant disease.     

Positron emission tomographic investigations of central muscarinic cholinergic receptors with three isomers of [76Br]BrQNP

We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[⁷⁶Br]BrQNP,E(-,-)-[⁷⁶Br]BrQNP andE(-,+)-[⁷⁶Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [⁷⁶Br]BrNH₄ and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M₂ selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M₁ selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., theE(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively.Z(-,-)-[⁷⁶Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for theE(-,+)-[⁷⁶Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors.Z(-,-)-[⁷⁶Br]BrQNP, which is displaced in higher amounts from M₂ mAChR-enriched structures, reveals an M₂ affinity. The two isomers having the (-,-)-configuration are potential probes for investigating central muscarinic receptors. The absolute configuration on the acetate chiral centre influences their muscarinic subtype selectivity and thecis-trans isomerism of the vinyl moiety affects their specific fixation.     

Small bowel transplantation: Effects on function of nonadrenergic, noncholinergic nerves

Previous work from our laboratory showed that spontaneous contractile activity of jejunal smooth muscle increases after small bowel transplantation. Our aim was to determine whether small bowel transplantation alters the function of nonadrenergic, noncholinergic (NANC) nerves. Seven groups of rats, (n ≥7 in each group) were studied as follows: 1 week after sham celiotomy and 1 week and 8 weeks after 45 minutes of ischemia/ reperfusion (IR1 and IR8), jejunal and ileal transection and reanastomosis (TR1 and TR8), or orthotopic small bowel transplantation (TX1 and TX8). Contractility of jejunal circular muscle strips was studied in vitro. Spontaneous contractile activity increased in the IR1, TR1, and TX1 and TX1 and TX8 groups (P<0.01). Under NANC conditions, spontaneous activity increased in TR1 and in both TX1 and TX8 (P<0.01) despite the lack of an increase in the frequency of contraction in TX1. Electrical field stimulation inhibited contractile activity at low frequencies, but under NANC conditions this inhibition persisted at higher frequencies. The calculated equieffective frequency (F₁₀₀) that produced a response equal to baseline contractile activity was similar in all groups, but under NANC conditions was greater in TX1 (P<0.025). Functional alterations of NANC nerves are partly responsible for the increase in spontaneous activity in rat jejunal circular muscle strips after a limited ischemia/reperfusion injury, after selective disruption of enteric neural continuity (transection/reanastomosis), and after small bowel transplantation. These findings may provide important insight into graft dysfunction after small bowel transplantation in humans. Supported by United States Public Health Service grant DK 39337 from the National Institutes of Health and by the Mayo Foundation.     

Local fibrinolysis for superior mesenteric artery thromboembolism

A 66-year-old man with atrial fibrillation was referred soon after developing left lower limb and abdominal pain with rectal bleeding. An immediate flush aortogram showed embolic occlusion of the left distal superficial femoral artery and superior mesenteric artery (SMA), 3 cm from its ostium. Recombinant tissue plasminogen activitor (rtPA) 40 mg was selectively in stilled in the SMA in two boluses. Abdominal symptoms resolved within 48 h, and complete recanalization of the SMA was shown on angiography. Exploratory laparotomy after 72 h showed a normal small bowel and right colon, and was completed by femoropopliteal embolectomy. Six months later, the patient remained asymptomatic.     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.