Experimental Search for Neutron to Mirror Neutron Oscillations as an Explanation of the Neutron Lifetime Anomaly.

An unexplained >4σ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons n into mirror neutrons n^{'}, part of a dark mirror sector, can increase the apparent neutron lifetime by 1% via a small mass splitting Δm between n and n^{'} inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy.

Compensating human subjects providing oocytes for stem cell research: 9-year experience and outcomes.

PURPOSE: Human oocytes are arguably one of the most important cell types in humans, yet they are one of the least investigated cells. Because oocytes are limited in number, the use of high-quality oocytes is almost entirely in reproduction. Furthermore, regulatory hurdles for research on gametes and regulations on funding related to research on gametes present significant obstacles to research and the advancement of reproductive treatments. Here we report the outcomes of the largest compensated oocyte donation program for research in the USA to date, and probably worldwide. METHODS: Women who participated in oocyte donation for research between 2008 and 2017 were contacted in a phone interview and completed a standardized questionnaire. RESULTS: Of 114 participants, 98 oocyte donors completed donation, donating 1787 mature MII oocytes and a total of 86 skin biopsies. Complication rate, including minor complications, of oocyte donation was 8/98, or 8.1%, for which two involved follow-up. Fifty-seven donors answered questions about their experience. Participants were incentivized primarily by money and a desire to help others and reported an overall favorable experience. Most, but not all, human subjects recalled that they had donated for research, and approximately half recalled that their oocytes were being used specifically for stem cell research. CONCLUSIONS: Compensated oocyte donation provides a reliable path to obtaining high-quality oocytes for research and is reviewed favorably by oocyte donors. The continuation of programs that offer compensation for oocyte donation is invaluable to continued progress and advancements in stem cell research and human embryology, and for the advancement of novel reproductive treatments.

Barrett's esophagus in Latinos undergoing endoscopy for gastroesophageal reflux disease symptoms.

Previous studies comparing the prevalence of Barrett's esophagus in Latinos and non-Latino whites are inconsistent. The aim of the study is to compare the prevalence of Barrett's esophagus in Latinos and non-Latino whites and to determine risk factors associated with Barrett's esophagus. Between March 2005 and January 2009, consecutive Latino and non-Latino white patients who underwent endoscopy for primary indication for symptoms of gastroesophageal reflux disease were identified by examining the internal endoscopy database at Los Angeles County + USC Medical Center. Barrett's esophagus was defined by columnar-lined distal esophagus on endoscopy confirmed by intestinal metaplasia on histology. Clinical features and endoscopic findings were retrospectively reviewed. The mean age of the 663 patients was 50 ± 12 years, 30% were male, and 92% were Latino. Compared with non-Latino whites, Latinos had more females (72% vs. 46%; P = 0.0001) and more Helicobacter pylori infection (53% vs. 24%; P = 0.003) but less tobacco use (7% vs. 17%; P = 0.01). Overall, 10% (68/663) of all patients had Barrett's esophagus whereas the prevalence was 10% (62/611) among the Latinos and 12% (6/52) among the non-Latino whites (OR 0.9, 95% CI 0.4-2.1; P = 0.75). One patient in the Latino group had high-grade dysplasia. On multivariate analysis, male gender (AOR 2.3, 95% CI 1.4-4.1; P = 0.002), diabetes (AOR 2.2, 95% CI 1.1-4.5; P = 0.03), and age ≥55 years (AOR 2.2, 95% CI 1.3-3.8; P = 0.006) were independently associated with Barrett's esophagus; Latino ethnicity remained nonsignificant (AOR 1.1, 95% CI 0.4-2.7; P = 0.88). In Latinos undergoing endoscopy for gastroesophageal reflux disease symptoms, the prevalence of Barrett's esophagus was 10%, comparable with non-Latino white controls as well as the prevalence previously reported among Caucasians. In addition to established risk factors, diabetes was associated with Barrett's esophagus.

Effectiveness of a training program to increase the capacity of health care providers to provide HIV/AIDS care and treatment in Swaziland.

Implementation of HIV care and treatment programs in sub-Saharan Africa is a complex undertaking that requires training of health care providers (HCPs). Many sub-Saharan African countries have introduced training programs to build human resources for health. Evaluation of the ongoing trainings is warranted so that programs can be improved. The purpose of this study was to evaluate Baylor International Pediatric AIDS Initiative's (BIPAI) HCP training program in Swaziland. The specific aims were: (1) to assess coverage and delivery of the training program; and (2) to determine the impact of the training program on HCPs' knowledge about HIV and pediatric practices, attitudes toward HIV/AIDS patients, and self-efficacy to provide antiretroviral therapy (ART). The evaluation was a multimethod design with two types of data collection and analysis: (1) one-group pretest-posttest survey with 101 HCPs; and (2) semi-structured in-depth interviews with seven trainers from Baylor College of Medicine and 16 local HCPs in Swaziland. Quantitative data were analyzed using Stata Statistical Software version 8.2 for descriptive and multivariate analysis while factor analysis was done using Statistical Program for Social Sciences version 14. The transcribed interviews were analyzed using a didactic approach. Process evaluation showed that the training had good coverage, was delivered as intended, and improved as the work progressed. The training program led to a significant increase (p=0.0000) in HCPs' knowledge about HIV/AIDS, ART, and relevant clinical pediatrics practices between pretest (mean 68.7% SD 13.7) and post training (mean 84.0% SD 12.0). The training program also increased trainees' self-efficacy to provide ART and their attitudes toward AIDS patients (p=0.0000 and 0.02, respectively). In conclusion, BIPAI training program in Swaziland had good coverage of all health care facilities and HCPs in Swaziland. The training was effective in imparting knowledge and skills to HCPs and in their attitudes toward HIV/AIDS patients.

ABT-737, an inhibitor of Bcl-2 family proteins, is a potent inducer of apoptosis in multiple myeloma cells.

Disruption of pathways leading to programmed cell death plays a major role in most malignancies, including multiple myeloma (MM). ABT-737 is a BH3 mimetic small-molecule inhibitor that binds with high affinity to Bcl-2 and Bcl-xL, preventing the sequestration of proapoptotic molecules and shifting the cell survival/apoptosis balance toward apoptosis induction. In this study, we show that ABT-737 is cytotoxic to MM cell lines, including those resistant to conventional therapies, and primary tumor cells. Flow cytometric analysis of intracellular levels of Bcl-2 family proteins demonstrates a clear inversion of the Bax/Bcl-2 ratio leading to induction of apoptosis. Activation of the mitochondrial apoptosis pathway was indicated by mitochondrial membrane depolarization and caspase cleavage. Additionally, several signaling pathways known to be important for MM cell survival are disrupted following treatment with ABT-737. The impact of ABT-737 on survival could not be overcome by the addition of interleukin-6, vascular endothelial growth factor or insulin-like growth factor, suggesting that ABT-737 may be effective in preventing the growth and survival signals provided by the microenvironment. These data indicate that therapies targeting apoptotic pathways may be effective in MM treatment and warrant clinical evaluation of ABT-737 and similar drugs alone or in combination with other agents in the setting of MM.

Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation.

Heat shock transcription factor 1 (HSF1) is constitutively expressed in mammalian cells and negatively regulated for DNA binding and transcriptional activity. Upon exposure to heat shock and other forms of chemical and physiological stress, these activities of HSF1 are rapidly induced. In this report, we demonstrate that constitutive phosphorylation of HSF1 at serine residues distal to the transcriptional activation domain functions to repress transactivation. Tryptic phosphopeptide analysis of a collection of chimeric GAL4-HSF1 deletion and point mutants identified a region of constitutive phosphorylation encompassing serine residues 303 and 307. The significance of phosphorylation at serines 303 and 307 in the regulation of HSF1 transcriptional activity was demonstrated by transient transfection and assay of a chloramphenicol acetyltransferase reporter construct. Whereas the transfected wild-type GAL4-HSF1 chimera is repressed for transcriptional activity and derepressed by heat shock, mutation of serines 303 and 307 to alanine results in derepression to a high level of constitutive activity. Similar results were obtained with mutation of these serine residues in the context of full-length HSF1. These data reveal that constitutive phosphorylation of serines 303 and 307 has an important role in the negative regulation of HSF1 transcriptional activity at control temperatures.

Thymoglobulin targets multiple plasma cell antigens and has in vitro and in vivo activity in multiple myeloma.

Multiple myeloma is characterized by the proliferation of clonal plasma cells that have a heterogeneous expression of various cell surface markers, precluding successful use of monoclonal antibodies for therapeutic targeting of the tumor cell. Thymoglobulin (rabbit-derived polyclonal anti-thymocyte globulin), by virtue of its method of preparation, contains antibodies against several B-cell and plasma cell antigens and offers an attractive option for immunotherapy of myeloma. Here, we demonstrate potent anti-myeloma activity of the rabbit anti-thymocyte globulin preparation Thymoglobulin in vitro and in vivo in an animal model of myeloma. Thymoglobulin was able to induce dose- and time-dependent apoptosis of several myeloma cell lines, including those resistant to conventional anti-myeloma agents. Importantly, the anti-myeloma activity was preserved even when myeloma cells were grown with different cytokines demonstrating the ability to overcome microenvironment-mediated resistance. Thymoglobulin induced apoptosis of freshly isolated primary myeloma cells from patients. Using a competitive flow cytometric analysis, we were able to identify the potential antigen targets for Thymoglobulin preparation. Finally, in a plasmacytoma mouse model of myeloma, Thymoglobulin delayed the tumor growth in a dose-dependent manner providing convincing evidence for continued evaluation of this agent in the clinic in patients with myeloma, either alone or in combination with other agents.

The detection of viral genomes by polymerase chain reaction in the myocardium of pediatric patients with advanced HIV disease.

OBJECTIVES: The aim of this study was to investigate the frequency of viral nucleic acid detection in the myocardium of human immunodeficiency virus (HIV)-infected children to determine whether an association exists with the development of heart disease. BACKGROUND: As improved medical interventions increase the life expectancy of HIV-infected patients, increased incidences of myocarditis and dilated cardiomyopathy (DCM) are becoming more apparent, even in patients without clinical symptoms. METHODS: Myocardial samples were obtained from the postmortem hearts of 32 HIV-infected children and from 32 age-matched controls consisting of patients with structural congenital heart disease and no myocardial inflammation and no cardiac or systemic viral infection. The hearts were examined histologically and analyzed for the presence of viral sequences by polymerase chain reaction (PCR) or reverse transcription-PCR. RESULTS: Myocarditis was detected histologically in 11 of the 32 HIV-infected patients, and borderline myocarditis was diagnosed in another 13 cases. Infiltrates were confined to the epicardium in two additional hearts. Virus sequences were detected by PCR in 11 of these 26 cases (42.3%); adenovirus in 6, CMV in 3 and both adenovirus and CMV in 2. Two cases without infiltrates were also positive for adenovirus: one had congestive heart failure (CHF) and the other adenoviral pneumonia. No other viruses were detected by PCR, including HIV proviral DNA. All control samples were negative for all viruses tested. CONCLUSIONS: These data suggest that the presence of viral nucleic acid in the myocardium is common in HIV-infected children, and may relate to the development of myocarditis, DCM or CHF and may contribute to the rapid progression of HIV disease.

Parallel, solution phase synthesis of dihydropyridine miticides via a versatile multicomponent reaction.

A novel class of highly active dihydropyridine miticides was prepared using a multicomponent reaction process. The initial lead was rapidly optimized using solution phase parallel synthesis techniques and a positional scanning approach. Detailed structure-activity relationships were developed for the amino and carbonyl components of the molecule and used to select the best candidates for broad field testing. The chemistry, biology and toxicology of these compounds will be presented along with numerous structural variants of the reaction products.

The heat-shock response: regulation and function of heat-shock proteins and molecular chaperones.

Exposure of cells to stresses such as heat shock, oxidant injury and heavy metals causes an imbalance in protein metabolism which challenges the cell to respond rapidly, yet precisely, to minimize the deleterious effects of environmental and physiological stress. The heat-shock response, through the activation of HSFs, results in the elevated expression of heat-shock genes and the concomitant synthesis of HSPs and molecular chaperones. Molecular chaperones function in a variety of protein biosynthetic events and protect proteins from the deleterious effects of acute or chronic stress by stabilizing and refolding protein-folding intermediates or facilitating protein degradation. The accumulation of misfolded proteins has also become a central issue to diseases of protein folding, including sickle cell haemoglobin, cystic fibrosis and prion diseases, in addition to complex multifactorial diseases such as bacterial and viral infections, myocardial ischaemia, neurodegenerative diseases and cancer.

Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma.

We investigated whether differences in IL-6 and IL-1beta expression could be detected in monoclonal plasma cells from patients with MGUS or MM. Expression of IL-6 and IL-1beta in bone marrow cells was determined using cell sorting to enrich for plasma cells followed by reverse transcriptase/polymerase chain reaction (RT/PCR). Nineteen patients (six MGUS, two primary amyloid (AL), 11 MM) were studied. IL-6 mRNA expression was detectable in the sorted CD38+/CD45- plasma cell populations from 0/6 MGUS, 0/2 AL and 5/11 MM patients. All five MM patients with autocrine IL-6 expression demonstrated an elevated plasma cell labeling index. IL-1beta mRNA was detectable in the sorted CD38+/CD45- plasma cell populations from 1/6 MGUS, 0/2 AL and 10/11 MM patients. In situ hybridization (ISH) confirmed that the IL-1beta producing cells were plasma cells. In conclusion, autocrine production of IL-6 parallels a high labeling index and aberrant expression of IL-1beta correlates with the diagnosis of MM. Follow-up of IL-1beta-positive MGUS patients will determine whether aberrant expression of IL-1beta will predict those MGUS patients that will eventually progress to MM.

Follicle-stimulating hormone promotes histone H3 phosphorylation on serine-10.

FSH promoted the rapid phosphorylation of the nuclear protein histone H3 in immature rat ovarian granulosa cells under experimental conditions that lead to cellular differentiation and not proliferation. FSH-stimulated histone H3 phosphorylation correlated with cAMP-dependent protein kinase A (PKA) activation and translocation of the PKA catalytic subunit to a nuclear-enriched fraction and was inhibited by the PKA inhibitor H89, and histone H3 phosphorylation was stimulated in cells treated with agents that raise intracellular cAMP levels such as forskolin and 8-bromo-cAMP. FSH-stimulated histone H3 phosphorylation in granulosa cells mapped to ser-10, a site previously identified as the PKA phosphorylation site in various mitotically active cells as the mitosis-specific phosphorylation site. Injection of the FSH analog PMSG to immature rats, which is known to stimulate granulosa cell proliferation as well as differentiation, also promoted histone H3 phosphorylation on ser-10 in granulosa cells. These results establish that FSH-stimulated histone H3 phosphorylation in granulosa cells is linked not only to granulosa cell mitosis but also to granulosa cell differentiation and that FSH-stimulated histone H3 phosphorylation on ser-10 in isolated granulosa cells is mediated by PKA. These results also identify the PKA-dependent histone H3 phosphorylation as an early nuclear protein marker for FSH-stimulated differentiation of granulosa cells. Based on the recently described function of histone H3 as a coactivator of transcription, these results are consistent with the hypothesis that phosphorylated histone H3 may facilitate PKA-dependent gene transcription in granulosa cells leading to the preovulatory phenotype.

Influence of polyamine architecture on the transport and topoisomerase II inhibitory properties of polyamine DNA-intercalator conjugates.

An efficient five-step synthetic method was developed to access a series of spermine derivatives containing appended acridine, anthracene, and 7-chloroquinoline motifs. The derivatives were composed of a spermine fragment covalently tethered at its N4 and N9 positions to an aromatic nucleus via an aliphatic chain (e.g., 8: acridine -[C4 aliphatic tether]-spermine-[C4 aliphatic tether]-acridine). The distance separating the spermine and aromatic nuclei was altered via different tethers composed of four or five methylene units. These bis ligands (8, 9, 12, and 13) were shown to inhibit human DNA topoisomerase II (topo II) activity at 5 microM. Enzymatic activity was assessed as the ability to unknot (decatenate) and cleave kinetoplast DNA (kDNA). Polyamine conjugation did not disrupt the ability of the acridine-spermine conjugates 8 and 9 to inhibit topo II activity as compared with the 9-aminoacridine and 9-(N-butyl)aminoacridine controls (at 5 microM). The parent polyamines, spermine (5 microM) and spermidine (10 microM), had little effect on topo II activity. In general, the bis-substituted spermine derivatives (8, 9, 12, and 13) were more efficient topo II inhibitors at 5 microM than their monosubstituted spermidine counterparts (22-25) at 10 microM. Within the bisintercalator spermine series, insertion of an additional methylene unit (i.e., C5 tethers) increased potency 2-fold (8, bis-C4-acridine, 47 h IC(50) = 40 microM; 9, bis-C5-acridine, IC(50) = 17 microM). Comparison of the bis- and monoacridine spermine motifs (8 and 17) revealed a 4-fold increase in potency for the latter architecture (94 h IC(50) for 8, 74 microM; for 17, 17 microM). In general the bisintercalators (8, 9, 12, and 13) behaved as cytostatic agents, while the monosubstituted acridine and anthracene derivatives (22-25) were cytotoxic. Anthracene-containing conjugates were generally more toxic than their acridine counterparts in an L1210 (murine leukemia) cell assay. Of the conjugates tested the (monointercalator)-spermine motif (e.g., 17) had the highest affinity for the L1210 polyamine transporter as revealed by spermidine protection experiments.

Combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus infection: pharmacokinetic properties, safety, and immunologic and virologic effects.

OBJECTIVES: To obtain preliminary information on the pharmacokinetic properties, tolerance, safety, and antiviral activity of combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus (HIV) infection. METHODS: Eight children (median age, 6.6 years; range, 2.8 to 12 years) with advanced HIV disease (median CD4 + lymphocyte count at baseline, 42 cells/ microL; range, 8 to 553 cells/microL) were treated with stavudine (2 mg/kg per day in two divided doses) and didanosine (180 mg/m2 per day in two divided doses) for 24 weeks. Seven children had histories of prior zidovudine therapy. All children had received stavudine alone for 19 to 33 months before the addition of didanosine to the treatment regimen. Children were assessed clinically and with laboratory studies at baseline, weekly through week 4 of combination therapy, and every 4 weeks thereafter. RESULTS: Analysis of stavudine and didanosine plasma half-life values, clearances, and area under the plasma concentration-versus-time curves revealed no obvious clinical pharmacokinetic interaction between the drugs through study week 12. Combination therapy was well tolerated, and there were no drug-associated clinical or laboratory adverse events. Signs and symptoms of peripheral neuropathy were not observed. All three children with baseline CD4 + lymphocyte counts greater than 50 cells/muL had greater than 20% increases in their counts within the first 12 weeks of therapy; CD4 + lymphocyte count increases were not observed in the other children. Plasma HIV RNA concentrations showed median declines of 0.88 log10 (range, -3.41 log10 to 0.31 log10) and 0.30 log10 (range, -0.63 log10 to 0.89 log10) at study weeks 12 and 24, respectively. CONCLUSIONS: Combination therapy with stavudine and didanosine was well tolerated and safe in this small group of children with advanced HIV disease. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. These findings should be confirmed, and the regimen's clinical efficacy should be examined, in controlled studies of HIV-infected children with less-advanced disease.

A phase I/II evaluation of stavudine (d4T) in children with human immunodeficiency virus infection.

OBJECTIVES: To determine the pharmacokinetic properties, tolerance, safety, and preliminary activity of stavudine in human immunodeficiency virus (HIV)-infected children. DESIGN: Phase I/II, open and dose-ranging (0.125 to 4 mg/kg/day in two divided doses). PATIENTS: Thirty-seven HIV-infected children (median age, 5.5 years; range, 7 months to 15 years) with a median CD4+ lymphocyte count at baseline of 242 cells/microL (range 2 to 2290 cells/microL). Thirty children had symptomatic HIV disease at entry; seven had HIV-related immunosuppression alone. Twenty-nine subjects had a history of prior zidovudine (ZDV) therapy. RESULTS: As compared with adults receiving the same weight-adjusted doses, the children we studied had lower maximum observed stavudine plasma concentrations (CMAX) and area under the plasma concentration versus time curves (AUC), and more rapid stavudine elimination. The absolute oral bioavailability of the drug ranged from 61% to 78%. There was no plasma accumulation of the drug between day 1 and week 12. Week 12 cerebrospinal fluid stavudine concentrations in seven subjects, obtained approximately 2 to 3 hours after oral doses, ranged from 16% to 97% of concomitant plasma concentrations. Stavudine was well-tolerated and there were no dose-related clinical or laboratory adverse events. One subject with baseline neurologic abnormalities experienced a transient episode of apparent pain or discomfort in her fingers, possibly related to stavudine. All other adverse events were attributed to underlying disease. Stavudine activity, measured indirectly by CD4+ lymphocyte count and serum p24 antigen concentration changes, was observed in some subjects. Progression of HIV disease and survival correlated with prior ZDV therapy, HIV disease classification, baseline CD4+ lymphocyte count, and weight growth velocity. CONCLUSIONS: Stavudine appears to hold promise for the treatment of HIV infection in children. Its pharmacokinetic properties are consistent and predictable, and it appears to be remarkably well-tolerated and safe. Although our study was not designed to assess the drug's efficacy, preliminary clinical and laboratory evidence of activity was observed.

Hysteroid dysphoria in depressed inpatients.

Hysteroid dysphoria has been described in outpatient populations and is thought to be a subtype of atypical depression involving rejection sensitivity and therapeutic response to monoamine oxidase inhibitors. The presence of hysteroid dysphoria was assessed, using a semistructured interview, in 18 depressed inpatients. The 6 patients who met the criteria for hysteroid dysphoria did not differ from other depressed patients in severity, premorbid adjustment, number of atypical features, or presence of melancholia. Implications for treatment are discussed.

Major depression and irritable bowel syndrome: is there a relationship?

BACKGROUND: Irritable bowel syndrome (IBS) has been reported in 10% to 22% of adults. Seventy percent to 90% of patients with IBS who seek medical attention have psychiatric comorbidity, most commonly major depression. In contrast, few studies have looked at the prevalence of IBS among psychiatric patients. METHOD: Using a semistructured clinical interview to study the prevalence of IBS, we compared 56 patients seeking treatment for major depression in an outpatient setting to an age- and sex-matched control group of patients (N = 40) who were seeking treatment in a general physician's office for other medical illnesses. The control group had no Axis I disorders. IBS was diagnosed according to the criteria of Drossman et al. RESULTS: Twenty-seven percent (N = 15) of patients with major depression met criteria for IBS in contrast to 2.5% (N = 1) of the control group (p = .0005). Patients with major depression and IBS were more likely to report symptoms of back pain, weakness, heartburn, and nocturnal bowel movements as well as a personal or family history of bowel disease compared with patients with major depression but without IBS. CONCLUSION: IBS is fairly common in patients seeking treatment for major depression. Prospective studies should address the question whether treatment of major depression leads to an improvement or resolution of the symptoms of IBS.

The role of aztreonam in treatment of complicated urinary tract infections in children.

Urinary tract infections are common among pediatric patients, occurring in approximately 2% of children within the first 5 to 10 years of life. Most urinary tract infections are uncomplicated and respond readily to treatment. However, complications may make treatment difficult and result in serious adverse sequelae. Several characteristics of aztreonam make it an attractive alternative to aminoglycosides and certain other antibiotics for the treatment of complicated urinary tract infections in children. It has been shown, for example, that the drug is highly active against most of the pathogenic organisms responsible for urinary tract infections in the pediatric population, as well as Pseudomonas aeruginosa and many less common, aminoglycoside- and cephalosporin-resistant Gram-negative bacteria. Aztreonam is widely distributed throughout the body and achieves potentially therapeutic concentrations in the kidneys and in urine for up to 24 hours after dosing. The efficacy and safety of this agent compare favorably with standard antibiotic agents. Aztreonam is associated with high rates of microbiologic and clinical cures, and the few side effects reported have been mild and transient.

Computed tomography in bacterial meningitis of childhood.

The hospital records of 85 children with bacterial meningitis were reviewed and a subset of 25 children who underwent computed tomography of the head were identified. The major stated indications for computed tomography were fever (8 patients), seizures (4 patients), signs of increased intracranial pressure (4 patients), focal neurologic dysfunction (3 patients) and recurrent meningitis (2 patients). Abnormal findings were demonstrated by computed tomography in 20 of 25 patients but in 8 patients consisted solely of nonspecific dilatation of spaces containing cerebrospinal fluid or of basilar enhancement. The yield of information that was useful either diagnostically or therapeutically was low; positive findings of obvious clinical relevance were present in only 2 cases. Computed tomography provides an accurate means of diagnosing intracranial complications of bacterial meningitis. It must be used conservatively, however, to limit expense and radiation exposure and enhance the yield of potentially relevant information. Computed tomography is indicated for children with persistent neurologic dysfunction, persistently positive cerebrospinal fluid cultures or recurrent meningitis, whereas it is of little value for children with prolonged fever alone.

Bacteremia in children afebrile at presentation to an emergency room.

Charts of 182 outpatient children with bacteremia caused by Streptococcus pneumoniae, Haemophilus influenza type b or Neisseria meningitidis were reviewed. Twenty-four patients (13%) were afebrile (temperature less than 37.8 degrees C) at presentation. Five afebrile patients had no history of fever. Four of the five had localizing signs of infection and one appeared toxic. Afebrile patients were not strikingly different from febrile bacteremic patients by any assessments. Bacteremia in children cannot be excluded on the basis of absence of fever by history and examination. Blood cultures should be performed on afebrile children who either have localizing signs of serious bacterial infection or appear toxic.