CBC and differential in VLBW infants

PURPOSE: This study tested the adequacy of established leukocyte indices in infants < or = 1,200 gm birth weight and < or = 32 weeks gestation. DESIGN: Charts of all admissions to the NICU from March 1991 through September 1994 were retrospectively reviewed. SAMPLE: All infants (n = 131) were outborn and admitted to the NICU within 24 hours after birth. MAIN OUTCOME VARIABLE: The leukocyte indices obtained during the first 72 hours after birth were plotted as a function of time in hours. RESULTS: Mode of delivery significantly affected total leukocyte count and absolute neutrophil count; sex and use of prenatal steroids did not. Ranges for total leukocyte count, absolute neutrophil count, and immature/total neutrophil (I:T) ratio demonstrate that normal values are variable and change over time. PRACTICE RECOMMENDATIONS: The wide distribution of values found, coupled with differences noted by mode of delivery, make normative data difficult to apply. The clinician must question the appropriateness of routinely obtaining a complete blood count and the clinical utility of the results.     

C6 modification of the pyridinone core of thrombin inhibitor L-374,087 as a means of enhancing its oral absorption

1 (L-374,087) is a potent, selective, efficacious, and orally bioavailable thrombin inhibitor that contains a core 3-amino-2-pyridinone moiety. Replacement of the C6 pyridinone methyl group of 1 by a propyl group gave 5 (L-375,052), which retained all the excellent properties of 1, and also yielded higher plasma levels after oral dosing in dogs and rats.     

Headache caused by a sphenoid mucocele but presenting as an ergotamine-induced headache

In a 65-year-old woman, symptomatic headache caused by a mucocele of the sphenoid sinus led to ergotamine abuse and subsequent ergotamine-induced headache. Since there were no neurological symptoms initially and the patient previously suffered from migraine, the mucocele was not recognized. Only after unsuccessful drug withdrawal therapy and an MRI, was the correct diagnosis made. Surgical removal of the mucocele led to complete relief of headache within 3 weeks. We conclude that ergotamine-induced headache can develop on the basis of symptomatic headache. In spite of the effectiveness of ergotamine tartrate, an MRI should be performed if focal neurological symptoms occur.     

Is acetylcholinesterase secreted from central neurons into the cerebral fluid?

Concretions of calcium carbonate normally appear every third and fourth da of the 4-da hamster cycle da 1 = day of ovulation). We presently found that the 2-da relation between ovulation and concretion formation was maintained even after ovulation was delayed 1 or more da by centrally acting drugs or by exposing the hamsters to constant light. It is therefore possible to identify days of ovulation in vaginal washing records of both normal and treated hamsters by counting back 2 da from each sequence of concretions.     

Tritium speciation in nuclear reactor bioshield concrete and its impact on accurate analysis

Tritium ((3)H) is produced in nuclear reactors via several neutron-induced reactions [(2)H(n, gamma)(3)H, (6)Li(n, alpha)(3)H, (10)B(n, 2alpha)(3)H, (14)N(n, (3)H)(12)C, and ternary fission (fission yield <0.01%)]. Typically, (3)H is present as tritiated water (HTO) and can become adsorbed into structural concrete from the surface inward where it will be held in a weakly bound form. However, a systematic analysis of a sequence of subsamples taken from a reactor bioshield using combustion and liquid scintillation analysis has identified two forms of (3)H, one weakly bound and one strongly bound. The strongly bound tritium, which originates from neutron capture on trace lithium ((6)Li) within mineral phases, requires temperatures in excess of 350 degrees C to achieve quantitative recovery. The weakly bound form of tritium can be liberated at significantly lower temperatures (100 degrees C) as HTO and is associated with dehydration of hydrous mineral components. Without an appreciation that two forms of tritium can exist in reactor bioshields, the (3)H content of samples may be severely underestimated using conventional analytical approaches. These findings exemplify the need to develop robust radioactive waste characterization procedures in support of nuclear decommissioning programs.     

Accumulation of COGEMA-La Hague-derived reprocessing wastes in French salt marsh sediments

Over the past five decades, authorized low-level discharges from coastal nuclear facilities have released significant quantities of artificial radionuclides into the marine environment. In northwest Europe, the majority of the total discharge has derived from nuclear reprocessing activities at Sellafield in the United Kingdom and COGEMA-La Hague in France. At the Sellafield site, a significant amount of the discharges has been trapped in offshore fine sediment deposits, and notably in local coastal and estuarine sediments, and much research has been focused on understanding the distribution, accumulation, and reworking of long-lived radionuclides in these deposits. In contrast, there are few high-resolution published data on the vertical distribution of radionuclides in fine-grained estuarine sediments near, and downstream of, COGEMA-La Hague. This paper therefore examines the vertical distribution of a range of anthropogenic radionuclides in dated salt marsh cores from two estuaries, one adjacent to, and the other downstream of, the COGEMA-La Hague discharge point (the Havre de Carteret at Barneville-Carteret and the Baie de Somme, respectively). The radionuclides examined show a vertical distribution which predominantly reflects variations in input from COGEMA-La Hague (albeit much more clearly at Barneville-Carteret than at the Baie de Somme site), and Pu isotopic ratios are consistent with a La Hague, rather than weapons' fallout, source. Because of sediment mixing, the marshes apparently retain an integrated record of the La Hague discharges, rather than an exact reproduction of the discharge history. Sorption of radionuclides increases in the order 90Sr < 137Cs < 60Co < 239,240Pu, which is consistent with Kd values reported in the literature. In general, the radionuclide activities observed at the sites studied are low (particularly in comparison with salt marsh sediments near the Sellafield facility), but are similar to those found in areas of fine sedimentation in the central Channel. These marshes are not major sinks for discharged reprocessing wastes.     

The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus

The GTPase Ran is essential for nuclear import of proteins with a classical nuclear localization signal (NLS). Ran's nucleotide-bound state is determined by the chromatin-bound exchange factor RCC1 generating RanGTP in the nucleus and the cytoplasmic GTPase activating protein RanGAP1 depleting RanGTP from the cytoplasm. This predicts a steep RanGTP concentration gradient across the nuclear envelope. RanGTP binding to importin-beta has previously been shown to release importin-alpha from -beta during NLS import. We show that RanGTP also induces release of the M9 signal from the second identified import receptor, transportin. The role of RanGTP distribution is further studied using three methods to collapse the RanGTP gradient. Nuclear injection of either RanGAP1, the RanGTP binding protein RanBP1 or a Ran mutant that cannot stably bind GTP. These treatments block major export and import pathways across the nuclear envelope. Different export pathways exhibit distinct sensitivities to RanGTP depletion, but all are more readily inhibited than is import of either NLS or M9 proteins, indicating that the block of export is direct rather than a secondary consequence of import inhibition. Surprisingly, nuclear export of several substrates including importin-alpha and -beta, transportin, HIV Rev and tRNA appears to require nuclear RanGTP but may not require GTP hydrolysis by Ran, suggesting that the energy for their nuclear export is supplied by another source.