Early Pulse Oximetry Data Improves Prediction of Death and Adverse Outcomes in a Two-Center Cohort of Very Low Birth Weight Infants.

BACKGROUND: We previously showed, in a single-center study, that early heart rate (HR) characteristics predicted later adverse outcomes in very low birth weight (VLBW) infants. We sought to improve predictive models by adding oxygenation data and testing in a second neonatal intensive care unit (NICU). METHODS: HR and oxygen saturation (SpO2) from the first 12 hours and first 7 days after birth were analyzed for 778 VLBW infants at two NICUs. Using multivariate logistic regression, clinical predictive scores were developed for death, severe intraventricular hemorrhage (sIVH), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (tROP), late-onset septicemia (LOS), and necrotizing enterocolitis (NEC). Ten HR-SpO2 measures were analyzed, with first 12 hours data used for predicting death or sIVH and first 7 days for the other outcomes. HR-SpO2 models were combined with clinical models to develop a pulse oximetry predictive score (POPS). Net reclassification improvement (NRI) compared performance of POPS with the clinical predictive score. RESULTS: Models using clinical or pulse oximetry variables alone performed well for each outcome. POPS performed better than clinical variables for predicting death, sIVH, and BPD (NRI > 0.5, p < 0.01), but not tROP, LOS, or NEC. CONCLUSION: Analysis of early HR-SpO2 characteristics adds to clinical risk factors to predict later adverse outcomes in VLBW infants.

Family Nurture Intervention in preterm infants alters frontal cortical functional connectivity assessed by EEG coherence.

AIM: To assess the impact of Family Nurture Intervention (FNI) on cortical function in preterm infants at term age. METHODS: Family Nurture Intervention is a NICU-based intervention designed to establish emotional connection between mothers and preterm infants. Infants born at 26-34 weeks postmenstrual age (PMA) were divided into two groups, standard care (SC, N = 49) and FNI (FNI, N = 56). Infants had EEG recordings of ~one hour duration with 124 lead nets between 37 and 44 weeks PMA. Coherence was measured between all pairs of electrodes in ten frequency bands. Data were summarised both within and between 12 regions during two sleep states (active, quiet). RESULTS: Coherence levels were negatively correlated with PMA age in both groups. As compared to SC infants, FNI infants showed significantly lower levels of EEG coherence (1-18 Hz) largely within and between frontal regions. CONCLUSION: Coherence in FNI infants was decreased in regions where we previously found robust increases in EEG power. As coherence decreases with age, results suggest that FNI may accelerate brain maturation particularly in frontal brain regions, which have been shown in research by others to be involved in regulation of attention, cognition and emotion regulation; domains deficient in preterm infants.

Developmental profiles of infant EEG: overlap with transient cortical circuits.

OBJECTIVE: To quantify spectral power in frequency specific bands and commonly observed types of bursting activities in the EEG during early human development. METHODS: An extensive archive of EEG data from human infants from 35 to 52 weeks postmenstrual age obtained in a prior multi-center study was analyzed using power spectrum analyses and a high frequency burst detection algorithm. RESULTS: Low frequency power increased with age; however, high frequency power decreased from 35 to 45 weeks. This unexpected decrease was largely attributable to a rapid decline in the number of high frequency bursts. CONCLUSIONS: The decline in high frequency bursting activity overlaps with a developmental shift in GABA's actions on neurons from depolarizing to hyperpolarizing and the dissolution of the gap junction circuitry of the cortical subplate. SIGNIFICANCE: We postulate that quantitative characterization of features of the EEG unique to early development provide indices for tracking changes in specific neurophysiologic mechanisms that are critical for normal development of brain function.

Reduced functional connectivity in visual evoked potentials in children with autism spectrum disorder.

OBJECTIVE: An analysis of EEG synchrony between homologous early visual areas tested the hypothesis that interhemispheric functional connectivity during visual stimulation is reduced in children with autism compared to controls. METHODS: EEG power and coherence within and between two homologous regions of the occipital cortex were measured during long latency flash visual evoked potentials. Measures were compared between two groups of children (5.5-8.5years), one with autism spectrum disorders and the other with typical development. RESULTS: In and below the theta band, interhemispheric synchrony was reduced in autistic subjects compared to typical controls by as much as 50%. Above the theta band interhemispheric synchrony in autistic children became indistinguishable from what would occur for uncorrelated cortical activity. Interhemispheric synchrony in autistic subjects was decreased in spite of bilaterally increased power. Wavelet power showed autistic children had a more rapid initial response to stimulation, a slower recovery, and more modulation at longer latencies. CONCLUSIONS: Results suggest that the sensory cortices of autistic children are hypersensitive to stimulation with concurrent diminished functional connectivity between hemispheres. SIGNIFICANCE: Simultaneously increased intrahemispheric power and decreased interhemispheric synchronization of elementalvisual information suggests either that power increases cause poor interhemispheric connectivity or that processes, such as thalamocortical regulation, impact power and coherence independently.

Cortical abnormalities in epilepsy revealed by local EEG synchrony.

Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or "hypersynchrony" which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation.

Origin binding protein-containing protein-DNA complex formation at herpes simplex virus type 1 oriS: role in oriS-dependent DNA replication.

Initiation of herpes simplex virus type 1 (HSV-1) DNA replication during productive infection of fibroblasts and epithelial cells requires attachment of the origin binding protein (OBP), one of seven essential virus-encoded DNA replication proteins, to specific sequences within the two viral origins, oriL and oriS. Whether initiation of DNA replication during reactivation of HSV-1 from neuronal latency also requires OBP is not known. A truncated protein, consisting of the C-terminal 487 amino acids of OBP, termed OBPC, is the product of the HSV UL8.5 gene and binds to origin sequences, although OBPC's role in HSV DNA replication is not yet clear. To characterize protein-DNA complex formation at oriS in cells of neural and nonneural lineage, we used nuclear extracts of HSV-infected nerve growth factor-differentiated PC12 and Vero cells, respectively, as the source of protein in gel shift assays. In both cell types, three complexes (complexes A, B, and C) which contain either OBP or OBPC were shown to bind specifically to a probe which contains the highest-affinity OBP binding site in oriS, site 1. Complex A was shown to contain OBPC exclusively, whereas complexes B and C contained OBP and likely other cellular proteins. By fine-mapping the binding sites of these three complexes, we identified single nucleotides which, when mutated, eliminated formation of all three complexes, or complexes B and C, but not A. In transient DNA replication assays, both mutations significantly impaired oriS-dependent DNA replication, demonstrating that formation of OBP-containing complexes B and C is required for efficient initiation of oriS-dependent DNA replication, whereas formation of the OBPC-containing complex A is insufficient for efficient initiation.

ICP0, ICP4, or VP16 expressed from adenovirus vectors induces reactivation of latent herpes simplex virus type 1 in primary cultures of latently infected trigeminal ganglion cells.

In a previous study, we demonstrated that infected-cell polypeptide 0 (ICP0) is necessary for the efficient reactivation of herpes simplex virus type 1 (HSV-1) in primary cultures of latently infected trigeminal ganglion (TG) cells (W. P. Halford and P. A. Schaffer, J. Virol. 75:3240-3249, 2001). The present study was undertaken to determine whether ICP0 is sufficient to trigger HSV-1 reactivation in latently infected TG cells. To test this hypothesis, replication-defective adenovirus vectors that express wild-type and mutant forms of ICP0 under the control of a tetracycline response element (TRE) promoter were constructed. Similar adenovirus vectors encoding wild-type ICP4, wild-type and mutant forms of the HSV-1 origin-binding protein (OBP), and wild-type and mutant forms of VP16 were also constructed. The TRE promoter was induced by coinfection of Vero cells with the test vector and an adenovirus vector that expresses the reverse tetracycline-regulated transactivator in the presence of doxycycline. Northern blot analysis demonstrated that transcription of the OBP gene in the adenovirus expression vector increased as a function of doxycycline concentration over a range of 0.1 to 10 microM. Likewise, Western blot analysis demonstrated that addition of 3 microM doxycycline to adenovirus vector-infected Vero cells resulted in a 100-fold increase in OBP expression. Wild-type forms of ICP0, ICP4, OBP, and VP16 expressed from adenovirus vectors were functional based on their ability to complement plaque formation in Vero cells by replication-defective HSV-1 strains with mutations in these genes. Adenovirus vectors that express wild-type forms of ICP0, ICP4, or VP16 induced reactivation of HSV-1 in 86% +/- 5%, 86% +/- 5%, and 97% +/- 5% of TG cell cultures, respectively (means +/- standard deviations). In contrast, vectors that express wild-type OBP or mutant forms of ICP0, OBP, or VP16 induced reactivation in 5% +/- 5%, 8% +/- 0%, 0% +/- 0%, and 13% +/- 6% of TG cell cultures, respectively. In control infections, an adenovirus vector expressed green fluorescent protein efficiently in TG neurons but did not induce HSV-1 reactivation. Therefore, expression of ICP0, ICP4, or VP16 is sufficient to induce HSV-1 reactivation in latently infected TG cell cultures. We conclude that this system provides a powerful tool for determining which cellular and viral proteins are sufficient to induce HSV-1 reactivation from neuronal latency.

The Altemeier repair: outpatient treatment of rectal prolapse.

PURPOSE: Rectal prolapse typically occurs in elderly patients, who are often poor surgical candidates because of the presence of multiple comorbidities. Abdominal approaches to procidentia have low recurrence rates but are associated with higher rates of morbidity and mortality. Perineal rectosigmoidectomy (Altemeier repair) is a safe and effective approach to the treatment of rectal prolapse and can be done as an outpatient procedure. In this article, the results of a series of 63 consecutive Altemeier repairs are presented. METHODS: Between February 1993 and December 1999, 63 patients (61 females) underwent Altemeier repair of rectal prolapse. The mean patient age was 79 years. Preoperative, intraoperative, and postoperative data were collected and analyzed for all patients. RESULTS: Median follow-up was 20.8 months. Seventy percent of patients were given a regional or local anesthetic. The average resected specimen length was 11.6 cm, and 83 percent of anastomoses were stapled. Sixty-two percent of patients were discharged home on the day of surgery, and 80 percent were home within 24 hours. Complications occurred in 10 percent of patients, but there was no perioperative mortality. There was a 6.4 percent recurrence rate, and all recurrences were successfully treated with repeat Altemeier repair. All 63 patients had complete objective resolution of prolapse, and 87 percent had subjective improvement after repair. CONCLUSIONS: Altemeier repair of rectal prolapse is safe, produces minimal discomfort, and does not require a general anesthetic. It is ideally suited to be done on an outpatient basis, as was done in the majority of patients in our series. The recurrence rate is slightly higher than with abdominal resections, but morbidity and cost are lower, and repeat perineal resections are easily and safely performed.

Phosphorylation of the herpes simplex virus type 1 origin binding protein.

The herpes simplex virus type 1 (HSV-1) origin binding protein (OBP), the product of the UL9 gene, is one of seven HSV-encoded proteins required for viral DNA replication. OBP performs multiple functions characteristic of a DNA replication initiator protein, including origin-specific DNA binding and ATPase and helicase activities, as well as the ability to interact with viral and cellular proteins involved in DNA replication. Replication initiator proteins in other systems, including those of other DNA viruses, are known to be regulated by phosphorylation; however, the role of phosphorylation in OBP function has been difficult to assess due to the low level of OBP expression in HSV-infected cells. Using a metabolic labeling and immunoprecipitation approach, we obtained evidence that OBP is phosphorylated during HSV-1 infection. Kinetic analysis of metabolically labeled cells indicated that the levels of OBP expression and phosphorylation increased at approximately 4 h postinfection. Notably, when expressed from a transfected plasmid, a recombinant baculovirus, or a recombinant adenovirus (AdOBP), OBP was phosphorylated minimally, if at all. In contrast, superinfection of AdOBP-infected cells with an OBP-null mutant virus increased the level of OBP phosphorylation approximately threefold, suggesting that HSV-encoded viral or HSV-induced cellular factors enhance the level of OBP phosphorylation. Using HSV mutants inhibited at sequential stages of the viral life cycle, we demonstrated that this increase in OBP phosphorylation is dependent on early protein synthesis and is independent of viral DNA replication. Based on gel mobility shift assays, phosphorylation does not appear to affect the ability of OBP to bind to the HSV origins.

Rectal injury caused by a personal watercraft accident: report of a case.

PURPOSE: An original case of rectal injury after a personal watercraft accident is reported. Principles of rectal trauma management are discussed. METHODS: We present a case of a rectal injury after a fall from a personal watercraft. Rigid sigmoidoscopy and a water-soluble contrast enema documented a posterior rectal tear. The patient was managed by diversion, drainage, and administration of antibiotics. RESULTS: The patient's rectal tear healed without complication. CONCLUSION: To our knowledge, this is the first reported case of an injury to the rectum as a result of a personal watercraft accident. A high suspicion of rectal injury must be maintained in victims who have fallen from the back of a personal watercraft. Treatment of a rectal injury should follow the basic principles of drainage, diversion, and administration of antibiotics, but variations in traditional management may be appropriate. Finally, preventative methods including wearing protective clothing, and possible modification to the watercraft to reduce risk of injury should be considered.

Approach to the patient.

A systematic approach to the patient with anorectal complaints allows for an accurate and efficient diagnosis of the underlying problem. The process can be divided into the interview, the examination, treatment, and conveyance of information. Throughout this process, the patient must be reassured and made as comfortable as possible. A successful interaction with the patient leads to a diagnosis and a treatment plan that is acceptable to both the physician and the patient.

The single-stapled ileo pouch anal anastomosis: a reasonable compromise.

Minimal anal sphincter disruption and preservation of the transitional epithelium during ileal pouch anal anastomosis (IPAA) are believed to play important roles in improving functional outcome. As a result, many surgeons have abandoned the traditional mucosectomy in favor of a double-stapled technique. The natural history of the retained colonic epithelium that occurs with this approach is uncertain. The authors have employed a technique of single circular-stapled IPAA, which accomplishes both of the described goals, while insuring that all the colonic mucus is removed during mucosectomy. We present a series of patients (n = 39) undergoing IPAA with transanal mucosectomy and a circular stapled anastomosis. The series consists of 16 males and 23 females with a mean age of 33.4 +/- 1.7 years. Twenty-nine patients had temporary ileostomies (2 not closed yet), and 10 did not. Pelvic sepsis occurred in two patients. However, three (9%) patients developed anastomotic sinus tracts that delayed ileostomy closure. With a follow-up of 24.0 +/- 3.2 months, the mean number of bowel movements are: day 6.4 +/- 0.4; night 1.1 +/- 0.2. Continence has been good or excellent in 97 per cent of patients during the day and 86 per cent at night. Therefore, this series indicates that good to excellent functional results following IPAA in the vast majority of patients can be accomplished with a transanal mucosectomy and a single stapled IPAA anastomotic technique. These results are comparable with those obtained with the double stapling technique without risk of retained rectal mucosa. Therefore, this technique provides good functional results because of minimal anal sphincter stretching, while at the same time insuring removal of all abnormal colonic epithelium.

Bilateral pneumothorax, an unusual complication of laparoscopic surgery.

Even though there are few complications with endoscopic surgery, some are life threatening. Pneumothorax is among these complications. Timely recognition and rapid diagnosis is essential. This is a case of a routine laparoscopy that was complicated by bilateral pneumothorax, and its diagnosis and treatment.

Treatment of levator syndrome using high-voltage electrogalvanic stimulation.

Twenty patients diagnosed as having levator syndrome were treated with electrogalvanic stimulation (EGS). Many of these patients had previously been treated unsuccessfully with other methods. While 60 percent of patients had good or excellent response to EGS when assessed immediately after therapy, a subsequent telephone survey revealed that one third of this group experienced recurrence. Of the group of 20 patients, only five (25 percent) remained symptom-free. Though results in this study were less favorable than other reports, EGS may still serve as a valuable adjunct in the treatment of levator syndrome.

The role of preoperative colonoscopy in colorectal cancer.

Routine preoperative colonoscopy has been recommended for those patients with the diagnosis of colorectal cancer to identify synchronous polyps and/or cancers which might otherwise be undetected on barium enema or at the time of operation. It has been suggested that this approach may alter surgical therapy or follow-up. The charts of 98 patients who underwent preoperative colonoscopy solely for the purpose of detecting additional polyps or cancers prior to open surgical resection for colorectal cancer were retrospectively reviewed. All patients had biopsy or barium-enema evidence of colorectal cancer. Patients with familial polyposis or chronic ulcerative colitis were excluded. Synchronous cancers were detected in 7.1 percent of patients, and synchronous neoplastic polyps in 29 percent. Forty-three percent of synchronous cancers and 73 percent of synchronous neoplastic polyps would not have been included in the standard surgical resection for the index cancer if the additional information provided by colonoscopy had not been available. Surgical treatment and/or follow-up were altered in 33 percent of patients as a consequence of the colonoscopic evaluation. Colonoscopy prior to surgery for colorectal carcinoma is highly desirable and may potentially improve long-term survival.

Dietary requirements of subjects exposed to hyperbaric He-O2 conditions: effects of various levels of vitamin supplementation.

A 24-d growth study was conducted on rats exposed to ambient air, 11 ATA He-O2, or 21 ATA He-O2 conditions. The rats were fed either a standard diet or the standard diet supplemented with 25, 50, or 100% increase of all vitamins, or the last with an additional 50 or 100% increase of casein. Fat, as cod liver oil was increased 0.5, 1.0, or 2.0% of the diet as the vitamins were increased. The vitamin and fat-supplemented diets, with or without supplemental casein, were adequate to support normal growth of the rats exposed to 11 ATA but not 21 ATA He-O2 conditions. Urine excretion and water consumption were closely related and varied in accordance with the adequacy of the diet. Feed digestibility was not a limiting factor in determining the growth of the rats under the three environments. The composition of the rat carcasses varied minimally.

Dietary requirements of subjects exposed to hyperbaric He-O2 conditions: effects of supplementation with major nutrient groups.

A 4-week growth study was conducted to determine whether changes in the type of diet could adequately compensate for the increased demands made upon the body by the stresses associated with exposure to hyperbaric He-O2 conditions. A normal rat diet (Hegsted-Chang) was used as a standard diet. This diet was also modified by increasing the fat content 25%, mineral mixture 25%, casein 50%, or all vitamins (including cod liver oil) 50%, or by decreasing the casein portion 10% from the standard levels. The corn starch portion was adjusted appropriately to maintain isocaloric properties of the various test diets. Male Sprague-Dawley rats served as the experimental subjects and were exposed to 1 ATA room air, 11 ATA He-O2, or 21 ATA He-O2 environmental conditions. The rats fed fat-supplemented diets grew as well under 11 ATA He-O2--but not under 21 ATA He-O2 conditions--as those fed the standard diet and exposed to 1 ATA room-air conditions. The rats fed protein-supplemented diets grew as well under both hyperbaric conditions as the control rats. Although the rat growth under the hyperbaric conditions equaled that under control conditions, it was less efficient because more food was required to produce each 1 g of gain. Significant differences were also observed in the apparent digestibilities of the various diets and in the protein, fat, and mineral contents of the carcasses.