Patterns of recurrence of intussusception in children: a 17-year review

PURPOSE: Patterns of recurrence of intussusception (INT) were reviewed to determine whether changes in management have affected the rate and patterns of recurrence as well as long-term outcome in children with multiple (i. e., 2 or more) recurrences. MATERIALS AND METHODS: Review was done of 763 children with 876 intussusceptions, including (1) recurrence rate, (2) patterns of recurrence (number of and interval between recurrences), (3) reducibility, (4) pathologic lead points (PLP), (5) operative findings and (6) long-term follow-up in those with multiple recurrences. RESULTS: Above features (1)-(6) were the same in those managed with barium enema (1979-1985) and those managed with air enema (1985-1996). Overall recurrence rate was 9 %; 11 % with barium enema and 8 % with air enema. Sixty-nine patients had 113 recurrences: 47/69 (68 %) and 1 recurrence and 22/69 (32 %) had multiple recurrences. Multiple recurrences presented as isolated episodes or in clusters up to 8 years. Reducibility was 100 % for initial INT and 95 % for recurrent episodes; there were no perforations. Surgery, in 4 with irreducible recurrence, revealed no PLP. PLP were present in 5 (8 %): 2 (4 %) with 1 recurrence and 3 (14 %) with multiple recurrences. No pattern of recurrence was predictive for PLP. Long-term follow-up (up to 15 years) available in 11 with multiple recurrences revealed a favourable outcome. CONCLUSIONS: Rates and patterns of recurrence did not change with altered management. Because of the high reduction rate of recurrences, lack of perforation and favourable long-term follow-up, we recommend radiological reduction for recurrent INT. Multiple recurrences are not a contraindication. A careful search for PLP is mandatory. Surgery should be reserved for irreducible recurrences or for demonstrated PLP.     

Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease

Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.     

Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer's disease

We explored the constitutive expression, maturational regulation, and relation to kainic-acid-induced apoptosis of cyclooxygenase (COX)-2 mRNA in rat brain. In adult rats, COX-2 mRNA was expressed primarily in limbic structures. Constitutive COX-2 mRNA expression increased markedly between Postnatal Day 7 (P7) and P14, reaching adult levels by P21. Despite intense KA-induced seizures, no COX-2 mRNA induction was found before P14 in any brain region examined. During response to KA-induced seizures in adult brain, COX-2 mRNA induction paralleled temporally and overlapped anatomically the appearance of cellular morphological features of apoptosis in subsets of cells of the pyramidal neuron layer of the hippocampal formation, amygdaloid complex, and pyriform cortex. While COX-2 mRNA showed KA-induced elevation in the granule cell layer of the dentate gyrus, no detectable morphological features of apoptosis were found in this region. Finally, monotypic culture of rat corticohippocampal neurons confirmed the neuronal expression of COX-2 in vitro and revealed that COX-2 is induced during response to glutamate treatment, leading to neuron death. These studies may provide novel insights into the role of COX-2 and mechanisms of action of nonsteroidal anti-inflammatory drugs in Alzheimer's disease.     

A novel class of mosquitocidal delta-endotoxin, Cry19B, encoded by a Bacillus thuringiensis serovar higo gene

Construction of computational blood flow models from magnetic resonance (MR) scans of real arteries is a powerful tool for studying arterial hemodynamics. In this report we experimentally determine a lower bound for errors associated with such an approach, and present techniques for minimizing such errors. A known, simple three-dimensional geometry (cylindrical tube) was imaged using a commercial MR scanner, and the resulting images were used to construct finite element flow models. Computed wall-shear stresses were compared to known values and peak errors of 40-60% were found. These errors can be attributed to limited spatial resolution, image segmentation and model construction. A simple smoothing technique markedly reduced these peak errors. We conclude that smoothing is required in the construction of arterial models from in vivo MR images. If used appropriately, such images can be used to construct acceptably accurate computational models of realistic arterial geometries.     

Odorants differentially enhance phosphoinositide turnover and adenylyl cyclase in olfactory receptor neuronal cultures

Both the cAMP and the phosphoinositide (PI) second messenger systems have been implicated in olfactory signal transduction. We have developed a primary culture system of mammalian olfactory receptor neurons (ORNs; Ronnett et al., 1991a) to permit analysis of odorant-induced second messenger system activation in the intact ORN. The ability of a series of odorants to stimulate PI turnover and adenylyl cyclase was examined. All odorants stimulated both second messenger systems, although with differential potencies. Stimulation of PI turnover desensitized upon reexposure of cultures to odorant. The enhancement by single odorants of both adenylyl cyclase and PI turnover, but to varying degrees, affords a mechanism for increased specificity in olfactory signal transduction.     

Acute hemodynamic effects of pulsed delivery of low flow nasal nitric oxide in children with pulmonary hypertension

DNA duplex and dumbbells containing chemically active acylphosphate internucleotide groups were synthesized. To obtain these compounds the chemical ligation method was used. The acylphosphate group was inserted into a DNA duplex and dumbbells as a result of template-directed condensation of 5'-phosphate and especially introduced 3'-carboxy groups of oligonucleotides. 1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide (EDC) was used as a condensing agent. Oligonucleotides containing a carboxy group were obtained by the interaction of their 3'-phosphate with glycine methyl ester under the action of EDC, followed by ester hydrolysis. The yields of acylphosphate-containing double-stranded oligonucleotides achieved 15-25% depending on the structure of their precursors. It was shown that these compounds are acylating agents and are efficiently cleaved in near-physiological conditions under the action of ethylenediamine or N-methylimidazole. These results indicate that double-stranded oligonucleotides carrying acylphosphate internucleotide groups could constitute new crosslinking reagents for affinity modification of DNA recognizing proteins.     

Opioid receptor antagonist nalmefene stereospecifically inhibits glutamate release during global cerebral ischemia

The opioid receptor antagonist nalmefene improves cellular bioenergetics and attenuates the reduction in tissue glutamate levels after global cerebral ischemia/reperfusion. The latter finding suggests that nalmefene might inhibit glutamate release during ischemia. To test this hypothesis, we used microdialysis techniques to examine the effect of nalmefene pretreatment on extracellular excitatory amino acid levels during global cerebral ischemia in rats. Saline, (-)-nalmefene (20, 100 or 500 micrograms/kg) or the inactive nalmefene enantiomer (+)-nalmefene (100 micrograms/kg) were given 15 min prior to induction of ischemia using a multi-vessel occlusion model. Pretreatment with (-)-nalmefene decreased peak dialysate glutamate in a dose-dependent fashion as compared to saline-treated controls, whereas (+)-nalmefene had no effect. These results suggest that opioid receptors may modulate glutamate release during ischemia and that inhibition of excitatory amino acid release may contribute to the protective actions of opioid receptor antagonists in cerebral ischemia.     

Contrast-enhanced magnetic resonance imaging of the breast: interpretation guidelines

In the past decade, most studies have shown that in selected indications of breast imaging, the overall accuracy can be improved by the additional use of contrast-enhanced magnetic resonance imaging (MRI). The sensitivity of contrast-enhanced MRI for invasive malignancy is >98%; reported specificity, however, ranges from 37% to 97%. This range of values is predominantly caused by different patient preselection and interpretation criteria. Other factors, such as technique (e.g., choice of pulse sequence and echo time, slice thickness, reduction in artifacts, dosage of contrast agent, and methods for elimination of fat signal), hormonal influences (menstrual cycle and hormonal replacement therapy), and levels of verification, influence the accuracy and reproducibility of contrast-enhanced MRI. An appropriate application of MRI is highly desirable because of the increased costs of imaging, increased rates of biopsy due to false-positive results, and possibility of false-negative results caused by technical failures and interpretation errors. We present an overview of the sensible application and interpretation of contrast-enhanced MRI of the breast based on our experience and on published data.