Outcome of unsuspected pneumococcemia in children not initially admitted to the hospital

The records were reviewed of 97 episodes of unsuspected pneumococcemia in children not initially admitted to the hospital. Antimicrobial agents were prescribed at the first visit for 46 children; at the second visit 37 of them were improved and nine were not. No antimicrobial agents were prescribed at the first visit for 51; at the second visit 16 of these patients were improved and 35 were not. Pneumococcemia persisted in two treated children and in 13 untreated children. Meningitis was identified later in four children (two treated and two untreated). Although pneumococcemia in children may be a transient event, it may also persist or result in meningitis or other localized infections.     

Damage to cochlear efferents following AF64A intoxication

Damage to cochlear efferents in chinchillas was assessed using transmission electron microscopy following unilateral treatment with the cholinotoxin ethylcholine mustard aziridinium ion (AF64A). AF64A was diluted in artificial perilymph to concentrations ranging from 0.5 to 100 microM. Survival times ranged from 1 to 12 weeks. At concentrations above 10 microM, widespread damage was noted to efferent fibers within the inner spiral bundle (ISB), tunnel spiral bundle (TSB), tunnel radial fibers (TRF) and efferent terminals at the base of OHCs. This damage included degeneration of fibers and terminals, delamination of mitochondria, vacuolization, and loss of cell membrane. However, at high concentrations, non-specific damage was also noted as thinnings or discontinuities of the membrane of OHCs and afferent fibers. At concentrations between 3 and 10 microM, selective damage was observed to efferent fibers within the ISB, TSB, TRF, and to terminals at the base of the OHCs, with all other structures appearing normal. At concentrations of 0.5 and 1 microM, damage was limited to efferent fibers within the TSB and ISB below the inner hair cells. In general, insult was greatest to middle- and basal-turn efferents, and longer survival times did not produce greater damage to, or loss of, efferents. These data suggest that at low concentrations, AF64A produces a partial yet selective degeneration of cochlear efferents within both the medial and lateral tracts, and that at the lowest concentrations used in these studies, AF64A produces a preferential insult on lateral olivocochlear efferents.     

RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist

The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described.     

Digital perfusion, evaluated scintigraphically, and hoof wall growth in horses with chronic laminitis treated with egg bar-heart bar shoeing and coronary grooving

Nuclear scintigraphy was used to assess digital perfusion before and after treatment in 10 horses with clinical and radiographic evidence of chronic laminitis. Horses were evaluated for lameness, degree of distal phalanx rotation, and heel-toe hoof wall growth ratio, and randomly divided into two treatment groups. Group 1 horses received only egg bar-heart bar shoeing; Group 2 underwent egg bar-heart bar shoeing and coronary grooving. Horses were re-evaluated for digital perfusion, lameness, degree of distal phalanx rotation, and hoof wall growth at 6 week intervals over the 18 week follow-up period. Prior to treatment, relative scintigraphic activity at the dorsal laminar area was decreased and relative scintigraphic activity at the toe and adjacent solar area was increased. Egg bar-heart bar shoeing was associated with significantly increased dorsal laminar scintigraphic activity and significantly decreased solar scintigraphic activity over the 18 week period. Coronary grooving, in combination with egg bar-heart bar shoeing, resulted in a significantly lower heel-toe hoof wall growth ratio but did not enhance digital perfusion. Seven of 10 (70%) horses were responsive to treatment, defined as an improvement in lameness by at least one grade. Horses that were refractory to treatment had significantly lower dorsal laminar scintigraphic activity and higher palmar coronary scintigraphic activity prior to treatment than horses that responded to treatment. Our results are the first to demonstrate that egg bar-heart bar shoeing is associated with improved dorsal laminar perfusion, and support the use of this technique. In addition, we found that pre-treatment nuclear scintigraphy was predictive of clinical outcome in horses with chronic laminitis treated with corrective shoeing.     

Mapping a quantitative trait locus involved in melanotic encapsulation of foreign bodies in the malaria vector, Anopheles gambiae

A Plasmodium-refractory strain of Anopheles gambiae melanotically encapsulates many species of Plasmodium, whereas wild-type mosquitoes are usually susceptible. This encapsulation trait can also be observed by studying the response of refractory and susceptible strains to intrathoracically injected CM-Sephadex beads. We report the results of broad-scale quantitative trait locus (QTL) mapping of the encapsulation trait using the bead model system. Interval mapping using the method of maximum likelihood identified one major QTL, Pen1. The 13.7-cM interval containing Pen1 was defined by marker AGH157 at 8E and AGH46 at 7A on 2R. Pen1 was associated with a maximum LOD score of 9.0 and accounted for 44% of the phenotypic variance in the distribution of phenotypes in the backcross. To test if this QTL is important for encapsulation of Plasmodium berghei, F2 progeny were infected with P. berghei and evaluated for degree of parasite encapsulation. For each of the two markers that define the interval containing Pen1, a significant difference of encapsulation was seen in progeny with at least one refractory allele in contrast with homozygous susceptible progeny. These results suggest that Pen1 is important for melanotic encapsulation of Plasmodium as well as beads.