Factors predicting cerebral edema in young children with diabetic ketoacidosis and new onset type I diabetes

We have attempted to identify any characteristics which could be used to predict the development of cerebral edema in four children under 5 years of age with new onset insulin-dependent diabetes mellitus and diabetic ketoacidosis. We retrospectively analysed and compared the concentration of serum sodium (corrected for serum glucose value) and effective serum osmolality of these 4 children with values of 10 age-matched controls with new onset insulin-dependent diabetes mellitus who did not develop cerebral edema during treatment of diabetic ketoacidosis. The initial serum sodium values of the two groups were not statistically different. Patients who developed cerebral edema had lower initial serum glucose values and effective serum osmolality. During treatment, patients who developed cerebral edema had consistently lower mean serum sodium and osmolality than controls at each 4-h interval after the first 4 h of therapy. Serum sodium and osmolality declined progressively after the initiation of therapy in cerebral edema patients, while remaining stable in controls. These data suggest that children who develop cerebral edema during treatment for diabetic ketoacidosis initially may have a relatively normal serum osmolality and subsequently develop progressive hyponatremia and/or a trend of declining serum sodium before developing cerebral edema.     

Identification of benzene oxide as a product of benzene metabolism by mouse, rat, and human liver microsomes

Benzene is a ubiquitous environmental pollutant that is known to cause hematotoxicity and leukemia in humans. The initial oxidative metabolite of benzene has long been suspected to be benzene oxide (3,5- cyclohexadiene-1,2-oxide). During in vitro experiments designed to characterize the oxidative metabolism of [14C]benzene, a metabolite was detected by HPLC-radioactivity analysis that did not elute with other known oxidative metabolites. The purpose of our investigation was to prove the hypothesis that this metabolite was benzene oxide. Benzene (1 mM) was incubated with liver microsomes from human donors, male B6C3F1 mice, or male Fischer-344 rats, NADH (1 mM), and NADPH (1 mM) in 0.1 M sodium phosphate buffer (pH 7.4) and then extracted with methylene chloride. Gas chromatography-mass spectrometry analysis of incubation extracts for mice, rats, and humans detected a metabolite whose elution time and mass spectrum matched that of synthetic benzene oxide. The elution time of the benzene oxide peak was approximately 4.1 min, while phenol eluted at approximately 8 min. Benzene oxide also coeluted with the HPLC peak of the previously unidentified metabolite. Based on the 14C activity of this peak, the concentration of benzene oxide was determined to be approximately 18 microM, or 7% of total benzene metabolites, after 18 min of incubation of mouse microsomes with 1 mM benzene. The metabolite was not observed in incubations using heat- inactivated microsomes. This is the first demonstration that benzene oxide is a product of hepatic benzene metabolism in vitro. The level of benzene oxide detected suggests that benzene oxide is sufficiently stable to reach significant levels in the blood of mice, rats, and humans and may be translocated to the bone marrow. Therefore benzene oxide should not be excluded as a possible metabolite involved in benzene-induced leukemogenesis.      

High-dose cytarabine and mitoxantrone as salvage therapy for refractory non-Hodgkin's lymphoma

High-dose cytarabine alone or in combination with mitoxantrone has been shown to be active against refractory non-Hodgkin's lymphoma in therapeutic trials. We administered these two drugs to 16 patients with advanced and refractory non-Hodgkin's lymphoma. Cytarabine was administered at 3 g/m2 as a 2-h intravenous infusion every 12 h on days 1-4 (8 doses) and mitoxantrone at 6 mg/m2/day as a 1-h intravenous infusion on days 1-5. The clinical efficacy and toxicity were assessed according to the WHO criteria. Five patients (31%, 95% CI: 8-54%) attained complete remission and two had partial remission. In three of the five complete remission patients, the remission lasted for > 4 months. The remaining two patients had complete remission for only 1.3 months. Myelosuppression with subsequent infection was the major toxicity of this regimen. Severe leukopenia (WBC < 1000/microliter) lasted for an average of 20 days and thrombocytopenia (< 25000/microliter) 18 days. Five patients (31%) died of treatment-related complications: neutropenia-associated sepsis in three, pneumonia in one and electrolyte imbalance in one. Nonmyeloid toxicities included alopecia in 100% (19% Gr.2, 75% Gr.3), stomatitis in 88% (13% Gr.2, 31% Gr.3), hepatotoxicity in 38% (6% Gr.2, 6% Gr.3), dermatitis in 31% (19% Gr.2), CNS toxicity in 25% (6% Gr.2, 6% Gr.3), infection in 38% (13% Gr.3, 19% Gr.4) and chemical conjunctivitis in 6% (Gr.2). We conclude that a proportion of refractory non-Hodgkin's lymphoma cases will respond to high-dose cytarabine+mitoxantrone, but that the treatment seems too toxic to be acceptable as salvage therapy for refractory non-Hodgkin's lymphoma.      

直肠癌术前热疗、放疗及化疗的临床病理意义

目的　探讨直肠癌手术前热疗、放疗及化疗后临床病理特征。方法　 38例局部进展期直肠癌病例进行了手术前热疗、放疗及化疗。局部热疗采用SIGMA60热疗机 (BSD - 2 0 0 0 ) ,放疗总剂量为 45Gy。四氢叶酸 5 -FU全身化疗共 2个疗程。辅助治疗完成后 4～ 6周手术。结果　经过术前辅助治疗 ,肿瘤的直径平均缩小 35 .5 %。 4例 (1 0 .5 % )达到病理完全缓解 ,另外 2 7例 (71 .0 % )达到PR(癌细胞坏死率≥ 50 % ) ,总有效率达 81 .6 %。辅助治疗后淋巴结阳性率由 68.4 %降至 44 .7%。病理检查所有肿瘤均有不同程度的癌细胞变性、细胞结构破坏、肿瘤血管破坏、出血及大片凝固性坏死。瘢痕区域可见灶性钙化、再生上皮。结论　术前热疗、放疗及化疗可以使部分肿瘤获得病理完全缓解、缩小原发瘤、减少局部淋巴结转移率     

Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration

AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants in the AIMP1 gene have been reported as the underlying cause of autosomal recessive primary neurodegenerative disorder. Here, we present two consanguineous families from Pakistan and Iran, presenting with moderate to severe intellectual disability, global developmental delay, and speech impairment without neurodegeneration. By the combination of homozygosity mapping and next generation sequencing, we identified two homozygous missense variants, p.(Gly299Arg) and p.(Val176Gly), in the gene AIMP1 that co-segregated with the phenotype in the respective families. Molecular modeling of the variants revealed deleterious effects on the protein structure that are predicted to result in reduced AIMP1 function. Our findings indicate that the clinical spectrum for AIMP1 defects is broader than witnessed so far.     

The postcraniectomy site: CT appearance

The hospital records and computed tomographic (CT) scans of 124 postcraniectomy patients were reviewed. The normal CT appearance of the operative site was defined and referred to as the "meningogaleal complex" (MGC). The CT characteristics of postoperative infections, intraaxial tumor recurrences, extraaxial tumor recurrences, and the various forms of postoperative cerebrospinal fluid collections were identified and differentiated by comparison with the normal scans. Specifically, when compared with the "postoperative baseline" anatomy, smooth thickening of the MGC often indicated postoperative infection (six cases), while nodular thickening heralded recurrent extraaxial tumor (eight cases). Recurrent intraaxial tumor adjacent to the craniectomy site caused no change in the MGC itself. A knowledge of the normal postoperative appearance of the MGC as well as good communication with the neurosurgeon can allow earlier detection of postoperative complications.     

Ethmoid sinus disease: CT evaluation in 400 cases. Part I. Nonsurgical patients

The unique anatomy of the ethmoid sinuses makes it difficult to interpret "soft-tissue clouding," especially on plain films. The clinical significance of isolated or generalized soft-tissue disease within ethmoid cells is unclear, and the patterns of bone erosion or remodeling must be relied on in establishing a specific differential diagnosis. Of 400 patients studied, 186 had inflammatory disease and 214 had tumors. Squamous cell carcinomas, metastases, and a few aggressive sarcomas were found almost exclusively to have bone destruction, while 94% of the remaining neoplasms were characterized by cavity remodeling. Further differentiation was sometimes possible because of the pattern and degree of tumor enhancement. Of the neoplasms, only the minor salivary gland lesions and neuromas had nonhomogeneous enhancement. Malignant lesions cannot be diagnosed with computed tomography (CT) unless bone destruction is present. Similarly, although the significance of persistent, benign-appearing soft-tissue disease during chemotherapy is unclear, tumor must always be suspected, even after many months of a stable CT appearance.     

Creation of oral care flavours to deliver breath-freshening benefits

Objective:  Oral care products deliver breath freshening primarily via mechano-chemical cleaning or by antimicrobial active systems. Dental flavours provide taste benefits, and freshen breath mainly by sensorial masking. We aimed to determine whether flavours could deliver breath freshening in products by inhibiting bacterial volatile sulphide compound (VSC) production.
Subjects and methods:  Flavour materials were screened for inhibition of hydrogen sulphide formation by Klebsiella pneumoniae in vitro , grouped by efficacy, and data provided to flavourists. Flavours were formulated to maximize the content of VSC-effective ingredients and re-screened to confirm performance. Extensive, iterative testing of flavours identified reliable creative rules to deliver efficient inhibition of H₂S generation. Breath-freshening flavours in whole products were then tested in-house in a 'breath freshness panel'.
Main outcome measures:  Malodour of panellists (not preselected for malodour score) was scored before and after product use, on the 'Rosenberg' 0–5 scale, together with residual flavour score, by extensively trained judges. Products were tested in double-blind, crossover studies, and results analysed using ANOVA.
Results and conclusions:  Products flavoured using these rules delivered significantly greater breath freshening at 2 h than control products, and equivalent benefits to products containing 0.1% (w/w) triclosan or 0.2% (w/w) zinc sulphate.     

Recessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: evidence for a linked protective factor

Amyotrophic lateral sclerosis (ALS) is a progressive motor neurodegeneration resulting in paralysis and death from respiratory failure within 3-5 years. About 20% of familial cases are associated with mutations in the gene for copper/zinc superoxide dismutase ( SOD1 ), which catalyses the dismutation of the superoxide radical to hydrogen peroxide and oxygen. Experimental evidence suggests mutations act by a toxic gain of function but the mechanism is unknown. There are >60 known SOD1 mutations associated with ALS and all are dominant except for one in exon 4, a D90A substitution which is recessive. D90A pedigrees with dominant inheritance have now been reported and this apparent contradiction needs to be explained. We performed a worldwide haplotype study on 28 D90A pedigrees using six highly polymorphic microsatellite markers. We now show that all 20 recessive families share the same founder (alpha = 0.999), regardless of geographical location, whereas several founders exist for the eight dominant families (alpha = 0.385). This finding confirms that D90A can act in a dominant fashion in keeping with all other SOD1 mutations, but that on one occasion, a new instance of this mutation has been recessive. We propose a tightly linked protective factor which modifies the toxic effect of mutant SOD1 in recessive families.      

Aedes (Finlaya) japonicus (Diptera: Culicidae), a newly recognized mosquito in the United States: analyses of genetic variation in the United States and putative source populations

Introduction of potential disease vectors into a new geographic area poses health risks to local human, livestock, and wildlife populations. It is therefore important to gain understanding of the dynamics of these invasions, in particular its sources, modes of spread after the introduction, and vectorial potential. We studied the population genetics of Aedes (Finlaya) japonicus japonicus (Theobald), an Asian mosquito that was recognized for the first time in the United States in 1998. We examined patterns of genetic diversity using random amplified polymorphic DNA and sequences of ND4 of mtDNA by comparing samples from populations spanning the range of this mosquito in Japan (six samples) and the United States (nine samples) as well as specimens intercepted in New Zealand in 1999. We found geographically differentiated populations in Japan, indicating limited gene flow even on small spatial scales. In the United States, we found evidence of significant genetic differentiation between samples from New York, Connecticut, and New Jersey and those from mid-Pennsylvania and Maryland. We were unable to pinpoint the source location(s) in Japan, although some of the U.S. samples are genetically close to samples from south Honshu and western Kyushu. Further studies should include samples from Korean populations. Distinct genetic signatures in U.S. populations undergoing expansion suggest the possibility of local increases in genetic diversity if and where they meet.