Near-infrared spectroscopy during cardiopulmonary resuscitation for pediatric cardiac arrest: A prospective, observational study.

AIM: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge. METHODS: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020. Eligible patients had ≥30 s of rSO2 data recorded during CPR. We compared median rSO2 and percentage of rSO2 measurements above a priori thresholds for the entire event and the final five minutes of the CPR event between patients with and without ROSC and survival to discharge. RESULTS: Twenty-one patients with 23 CPR events were analyzed. ROSC was achieved in 17/23 (73.9%) events and five/21 (23.8%) patients survived to discharge. The median rSO2 was higher for events with ROSC vs. no ROSC for the overall event (62% [56%, 70%] vs. 45% [35%, 51%], p = 0.025) and for the final 5 minutes of the event (66% [55%, 72%] vs. 43% [35%, 44%], p = 0.01). Patients with ROSC had a higher percentage of measurements above 50% during the final five minutes of CPR (100% [100%, 100%] vs. 0% [0%, 29%], p = 0.01). There was no association between rSO2 and survival to discharge. CONCLUSIONS: Higher cerebral rSO2 during CPR for pediatric cardiac arrest was associated with higher rates of ROSC but not with survival to discharge.

Genomics and Marek's disease virus.

Marek's disease virus (MDV), a lymphotrophic alphaherpesvirus of chickens, causes a disease that is characterized by tumor formation, immunosuppression and neurological disorders. Recent developments in chicken genomics have been applied to studies of MDV and have advanced our understanding of both the virus and the disease it causes. We have constructed and used microarrays to identify host genes that are up-regulated in chicken embryo fibroblasts infected with MDV as a first step to catalog the host response to infection. An additional level of gene regulation lies at the level of microRNAs (miRNAs). miRNAs are a class of small (approximately 22 nt) regulatory molecules encoded by a wide variety of organisms, including some viruses, that block translation or induce degradation of specific mRNAs. Herpesviruses, which replicate in the nuclei of infected cells, are a particularly important class of viruses that express miRNAs. miRNAs from two of the oncogenic herpesviruses; namely, Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV) have been cataloged. We recently identified MDV-encoded miRNAs. One cluster of miRNAs flanks the meq oncogene, and a second cluster maps to the latency associated transcript (LAT) region of the genome. The LATs are encoded anti-sense to the ICP4 immediate early gene, and the meq gene, which is unique to pathogenic serotypes of MDV, is the most likely oncoprotein or co-oncoprotein encoded by MDV. The conservation of these sequences is suggestive of an important role in pathogenesis.

Detection of mutagens-carcinogens: carcinogen-induced lesions pinpointed by alkaline phosphatase activity in fixed gastric specimens from rats.

Alkaline phosphatase (AP) activity was not detectable by histochemical staining in the glandular stomachs of normal rats. However, AP activity was present at high levels in the brush borders of the intestine and persisted after fixation of the tissues in Formalin at room temperature. Foci of AP activity were detected in gross Formalin-fixed specimens of glandular stomachs of male and female inbred F344 rats exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and killed over 6 years ago. The incidence of AP-positive foci increased in proportion to the dose of the carcinogen MNNG. Histologically, most of the grossly visible AP-positive foci corresponded to areas of intestinal metaplasia and adenocarcinoma. AP-positive foci localized sites of pathologic significance for microscopic examination and pinpointed gastric sites containing very early tumors that were missed by standard examination.

Estrogen profiles in young women: effect of maternal history of breast cancer.

To examine the hypothesis that familial breast cancer risk is related to estrogen metabolism, we analyzed urines of daughters of breast cancer patients and their matched controls for estrone (E1), estradiol (E2), and estriol (E3). From this, we computed estriol proportions (E3/E1 + E2 + E3). "Patient-daughters" and the matched controls showed no differences in estriol proportions. Our results failed to support the hypothesis that high-risk women (those with a family history of breast cancer) have relatively lower estriol proportions, and we concluded that whatever family history contributes to breast cancer risk, that risk is not likely to be transmitted by the estrogen profile.

PIP: A study designed to test the hypothesis that daughters of breast cancer patients would have "less favorable" estriol proportions than would a group of otherwise similar controls is reported. Urinary estrogen profiles of 46 daughters born to 45 women who later developed breast cancer and of 46 controls were examined. Computed estriol proportions (estriol/estrone plus estradiol plus estriol) revealed no differences in "patient-daughters" and the matched controls. It is concluded that whatever family history contributes to breast cancer risk, that risk is not likely transmitted by the estrogen profile.

Aroclor 1254-induced intestinal metaplasia and adenocarcinoma in the glandular stomach of F344 rats.

Ingestion of diets containing Aroclor 1254, a mixture of polychlorinated biphenyls, for 2 years led to a dose-related increase in the incidence of focal lesions in the glandular stomachs of male and female F344 rats. The incidence of stomach lesions was 6% in control specimens and in specimens from rats fed a diet containing 25, 50, or 100 ppm Aroclor 1254, the incidences of stomach lesions were 10, 17, and 35%, respectively. The majority of gastric lesions in treated rats were histologically identified as intestinal metaplasia characterized by an architecture resembling that of intestinal crypts and particularly by goblet cells, which stained with Alcian blue and periodic acid-Schiff reagent. Adenocarcinomas were found in six specimens. Most (88%) of the lesions were located in the pyloric region of the glandular stomach. No multiple lesions were observed among 47 control specimens examined; however, nine cases of multiple lesions were observed in 30 lesion-containing specimens from Aroclor 1254-treated rats. Although the exact relationship between gastric intestinal metaplasia and adenocarcinoma remains to be established, they commonly coexist and may share initiating mechanisms.

Marek's disease virus latency.

MDV latency is defined as the persistence of the viral genome in the absence of production of infectious virus except during reactivation. A number of systems for studying MDV latency exist, and most involve the use of lymphoblastoid cells or tumors. It has been difficult to divorce latency and transformation. Understanding the relationship between these two states remains a major challenge for the MDV system. Based on their patterns of expression, the MDV LATs are apt to be important in the balance between latent and lytic infections. The LATs are a complex group of transcripts. The profile of gene expression that characterizes latency differs among all herpesviruses, and MDV is no exception. MDV LATs bear little resemblance to LATs of other alphaherpesviruses or to the LATs of other lymphotropic herpesviruses. LAT splicing patterns are complex and the relationships among various spliced species or between these species and the large 10-kb transcript are unknown. In addition, the existence of any protein gene products of significance is unknown at this time. More work is needed to further investigate the significance and function of these RNAs. Better technology to construct mutants in the MDV system is badly needed, since the analysis of mutants in the chicken is a powerful and unique advantage of the MDV system.

Artificial implants and soft tissue sarcomas.

The carcinogenic potential of artificial implants has been of concern in recent years. Case reports and animal studies, dating back to the 1950s, have reported possible associations between artificial implants and soft tissue sarcomas, but epidemiologic data have been lacking. In a recent study of soft tissue sarcomas and military service, data on artificial implants were collected but not presented. This paper examines a possible association between artificial implants and soft tissue sarcomas.

Chronic open-angle glaucoma and ocular hypertension. An epidemiological study.

An epidermiological study of patients with chronic simple glaucoma or ocular hypertension suggests that the diagnosis of glaucoma is associated with a positive family history, acute blood loss, and diabetes mellitus. There was no association with other vascular disease or with smoking. Ocular hypertension was related to smoking habits but not to family history. The relationship of these variables to ocular hypertension/glaucoma status is discussed.

Risk of endometrial cancer after tamoxifen treatment.

A total of 18 studies have been published concerning the possible relationship of tamoxifen to endometrial cancer. Findings range from a protective effect (RR = 0.47) to a risk ratio as high as 15.2. Most studies are based on previous clinical trials of the drug. There are several recurring biases throughout almost all of the studies reported to date. This paper provides a critical review of each of the studies, including identification of bias sources and potential confounding variables. A causal association has not been proven (nor even strongly indicated) for tamoxifen and endometrial cancer, and further investigation, with less bias, will be required to resolve the question.

Effects of chemical and physical mutagens on the frequency of a large genetic duplication in Salmonella typhimurium. II. Stimulation of duplication-loss from merodiploids.

Strains of Salmonella typhimurium which contain a duplication of approximately 30% of the genome may be obtained by a simple selective procedure. These strains are highly unstable, losing the duplication when grown on non-selective medium. In this paper we report that treatment of merodiploid bacteria with mutagenic agents stimulates the rate at which haploid segregants are obtained from merodiploid strains. The mutagens which have been tested for this effect are X-rays, ultraviolet light (UV), ethyl methanesulfonate (EMS), and the azaacridine half-mustard ICR-372.

Effects of chemical and physical mutagens on the frequency of a large genetic duplication in Salmonella typhimurium. I. Induction of duplications.

In Salmonella typhimurium a simple selection has been described to detect bacteria that are merodiploid for almost one-third of the chromosome. The selective procedure is based upon improved utilization of L-malate as the sole carbon source in merodiploid strains. The spontaneous frequency of the duplication in haploid strains is approximately 10(-4) per cell plated. Following the exposure of a haploid strain to mutagenic agents, there is a dose-dependent increase in the duplication frequency above the spontaneous level. In this paper we describe the induction of genetic duplications in Salmonella typhimurium by X-rays, ultraviolet light (UV), ethyl methanesulfonate (EMS), nitrous acid, and the azaacridine half mustard, ICR-372.

The solvent effects of calcium hydroxide irrigating solution on bovine pulp tissue.

The solvent effects of calcium hydroxide irrigating solution (used alone and in combination with sodium hypochlorite) on bovine pulp tissue were studied. Forty pieces of pulp tissue weighing 90 mg each were treated with calcium hydroxide solution alone, calcium hydroxide and sodium hypochlorite alternated, sodium hypochlorite alone, and saline alone. Each piece of tissue was treated for 32 min. Desiccated pretreatment and posttreatment weights were compared. There was no significant difference between the dissolution capability of calcium hydroxide solution used alone and of saline. No significant difference was noted between calcium hydroxide solution and sodium hypochlorite used alternately, and sodium hypochlorite used alone. However, both of these groups were significantly more effective at dissolving tissue than calcium hydroxide solution alone or saline. Calcium hydroxide solution was an ineffective solvent of pulpal tissue. If tissue dissolution is desired during root canal therapy, the use of calcium hydroxide solution as the sole irrigant is no more effective than saline.

A review of epidemiological studies on artificial sweeteners and bladder cancer.

Next to tobacco, saccharin may be the substance that has been most studied epidemiologically. Over 5000 patients with bladder cancer have participated in case-control studies; over 27,000 diabetics have been observed for 234,000 person-years. The summary relative risk from combining all case-control studies is less than 0.98, the standardized mortality ratio for bladder cancer in diabetics is only 70. Analysis of these studies leads to the conclusion that saccharin is not related to human bladder cancer.

Airborne carcinogens and human cancer.

There is as yet little convincing evidence that air pollution contributes to cancer risk, save for the strong suspicion of an increase in risk for persons living adjacent to arsenic emitters. The lack of any demonstrated direct and strong relationship between pollution and cancer, as well as the absence of any easily identifiable cancer epidemic in polluted areas, leads us to suspect that if a relationship exists, it is relatively weak and contributes little to the total cancer burden, especially in comparison to hazards such as cigarette smoking. There is a need for further research to verify our conclusions.

Efficacy in chickens of a herpesvirus of turkeys recombinant vaccine containing the fusion gene of Newcastle disease virus: onset of protection and effect of maternal antibodies.

The onset of protection against Newcastle disease and the effect of maternal antibodies to Newcastle disease virus (NDV) and Marek's disease virus (MDV) on vaccine efficacy were determined following vaccination of chickens with a recombinant herpesvirus of turkeys (HVT) vaccine expressing the fusion (F) glycoprotein gene of NDV. Onset of protection following intra-abdominal administration of the recombinant HVT/F vaccine at 1 day of age and subsequent ocular challenge with the neurotropic velogenic Texas GB strain of NDV was determined to occur between days 14 and 21 post-vaccination (PV). Vaccination with the Hitchner B1 strain of NDV resulted in protection by day 6 PV, and vaccination with an inactivated NDV oil-emulsion vaccine induced protection by day 14 PV. One-day-old broiler-type chickens with maternal antibodies to both NDV and MDV and 1-day-old specific-pathogen-free (SPF) white leghorn chickens lacking maternal antibodies were vaccinated with the recombinant HVT/F vaccine or with control vaccines, challenged intra-abdominally with the very virulent RB1B strain of MDV on day 8 PV, and challenged with the Texas GB strain of NDV on day 29 PV. The HVT/F and NDV strain Hitchner B1 vaccines provided 73% and 80% protection, respectively, against NDV in broilers, whereas both vaccines resulted in 100% protection in SPF leghorns.

Transfection of chicken embryo fibroblasts with Marek's disease virus DNA.

Total DNA from Marek's disease virus (MDV)-infected chicken embryo fibroblasts was transfected into freshly plated secondary chicken embryo fibroblasts using calcium phosphate-mediated transfection. Transfection frequencies were dose-dependent and non-linear. The maximum transfection frequencies of nine MDV DNA preparations using 8-25 micrograms total DNA ranged from 45 to 898 plaques per calcium phosphate/DNA precipitate. Approximately 100-200 plaques per 60-mm tissue-culture dish using 1-5 micrograms total DNA from MDV-infected chicken embryo fibroblasts were typically obtained. Transfection was most efficient when the pH of the HEPES buffer was 7.0, no additional carrier DNA was added to the precipitates, and the cultures were exposed for 3 minutes to 15% buffered glycerol 4 hours after the addition of the calcium phosphate/DNA precipitates.

Inhibition of Marek's disease virus DNA transfection by a sequence containing an alphaherpesvirus origin of replication and flanking transcriptional regulatory elements.

A co-transfection method was used to identify regions of the Marek's disease virus (MDV) genome that inhibit plaque formation when introduced along with total DNA from MDV-infected chicken embryo fibroblasts into secondary chicken embryo fibroblasts. Co-transfections involving MDV plasmids containing the BamHI-D or BamHI-H regions of the genome inhibited plaque formation more than 10-fold. The inhibitory region was localized to a 222-base-pair region that contains a sequence homologous to the consensus origin of replication of alphaherpesviruses. The region also contains several potential transcriptional regulatory elements, including two CCAAT boxes, one Sp1 binding site, and an octamer element. The sequence of this region has been reported previously. Transfection inhibition was also observed for the BamHI-I2 region, although the effect was weaker.

Coinfection of specific-pathogen-free chickens with Marek's disease virus (MDV) and chicken infectious anemia virus: effect of MDV pathotype.

Both Marek's disease virus (MDV) and chicken infectious anemia virus (CIAV) infections are prevalent in chickens throughout the world. In the past decade, MDV strains with increased virulence (very virulent plus MDV pathotype [vv+MDV]) have been isolated. The purpose of this experiment was to determine the effects of coinfection of chickens with CIAV and a vv+MDV isolate. Specific-pathogen-free chickens were inoculated at 1 day posthatch with RB1B (very virulent MDV pathotype [vvMDV]) only, 584A (vv+MDV) only, CIAV only, RB1B + CIAV, 584A + CIAV, or nothing. Samples of spleen, thymus, and bursa of Fabricius were collected at 4, 7, 10, and 13 days postinoculation (DPI). Thymic and bursal atrophy at 13 DPI and final mortality at 30 DPI were significantly greater in chickens inoculated with 584A with or without added CIAV, or with RB1B plus CIAV, compared with birds inoculated with RB1B alone. Both amounts of virus reisolated and levels of virus detected by quantitative-competitive polymerase chain reaction were greater at 4 DPI in 584A inoculates compared with RB1B inoculates. To monitor the early cytolytic infection, northern analysis was done with a probe for the MDV immediate early gene ICP4 (infected cell protein 4). In the absence of CIAV, ICP4 expression was more apparent in chickens inoculated with 584A than in those inoculated with RB1B. CIAV coinfection increased ICP4 expression in the spleens of chickens infected with RB1B. These results indicated that inoculation of chickens with the 584A isolate caused a more robust early cytolytic infection compared with inoculation with RB1B alone and support the classification of 584A as a vv+MDV strain. Coinfection with CIAV exacerbated vvMDV strain RB1B infection. The extent of this exacerbation was less evident when birds were coinfected with 584A and CIAV.

Protection of chickens from Newcastle and Marek's diseases with a recombinant herpesvirus of turkeys vaccine expressing the Newcastle disease virus fusion protein.

Recombinant strains of herpesvirus of turkeys (HVT) were constructed that contain either the fusion protein gene or the hemagglutinin-neuraminidase gene of Newcastle disease virus (NDV) inserted into a nonessential gene of HVT. Expression of the NDV antigens was regulated from a strong promoter element derived from the Rous sarcoma virus long terminal repeat. Recombinant HVT strains were stable and fully infectious in cell culture and in chickens. Chickens receiving a single intra-abdominal inoculation at 1 day of age with recombinant HVT expressing the NDV fusion protein had an immunological response and were protected (> 90%) against lethal intramuscular challenge at 28 days of age with the neurotropic velogenic NDV strain Texas GB. Recombinant HVT expressing the NDV hemagglutinin-neuraminidase provided partial protection (47%) against the same challenge. Chickens vaccinated with recombinant HVT vaccines had low levels of protection against NDV replication in the trachea when challenged ocularly. Recombinant HVT vaccines and the parent HVT strain provided similar levels of protection to chickens challenged with the very virulent RB1B strain of Marek's disease virus, indicating that insertion of foreign sequences into the HVT genome did not compromise the ability of HVT to protect against Marek's disease.

A monoclonal antibody to ICP4 of MDV recognizing ICP4 of serotype 1 and 3 MDV strains.

Monoclonal antibodies (MAbs) were prepared against ICP4 of Marek's disease virus (MDV). Mice were inoculated with ICP4 obtained from High-Five insect cells infected with a recombinant baculovirus expressing ICP4. MAbs were selected by enzyme-linked immunosorbent assay (ELISA) using MDV-infected and control chick kidney cells as antigens. One of the MAbs, 5H8, recognized an epitope toward the carboxyl terminus of ICP4 based on staining of reticuloendotheliosis virus-transformed cells transfected with full-length and truncated ICP4 constructs. This MAb recognized ICP4 in chicken embryo fibroblasts (CEFs) infected with MDV strains JM16 and HVT but not with SB-1 strain. Using Western blot analysis a protein of 155 kDa was detected in CEFs infected with JM16 and HVT strains.