Search

Purpose: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome., Methods: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants., Results: The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS)., Conclusion: The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use., Competing Interests: Conflict of Interest SEP is a member of the scientific advisory panel of Baylor Genetics Laboratories. All other authors declare no conflicts of interest. Ethics Declaration This study was conducted in accordance with the guidelines of the Ethics Committee of the Medical Faculty of the University of Bonn and the 1975 Declaration of Helsinki. Participants of clinical genetic testing gave written informed consent for their data to be used for clinical research and genetic investigations according to local regulations., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Li-Fraumeni syndrome, caused by germline pathogenic variants in TP53, results in susceptibility to multiple cancers. Variants of uncertain significance (VUS) and reclassification of variants over time pose management concerns given improved survival with cancer surveillance for LFS patients. We describe the experience of TP53 variant reclassification at a pediatric cancer center., Methods: We reviewed medical records (2010-2019) of 756 patients seen in Texas Children's Cancer Genetics Clinic. We noted initial TP53 classification and any reclassifications. We then classified TP53 variants following ClinGen TP53 variant curation expert panel recommendations using data from ClinVar, medical literature and IARC database., Results: Of 234 patients tested for TP53, 27 (11.5%) reports contained pathogenic/likely pathogenic (P/LP) variants and 7 (3)% contained VUS. By January 2022, 4 of 6 unique VUS and 2 of 16 unique P/LP variants changed interpretations in ClinVar. Reinterpretation of these 4 VUS in ClinVar matched clinical decision at the time of initial report. Applying TP53 VCEP specifications classified 3 VUS to P/LP/benign, and one pathogenic variant to likely benign., Conclusions: Planned review of variant significance is essential, especially for patients with high probability of LFS., Competing Interests: Conficts of interest Sharon Plon is a member of the Scientific Advisory Panel of Baylor Genetics Laboratories. There are no other conflicts of interest to report., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Genomic testing is routinely utilized across clinical settings and can have significant variant interpretation challenges. The extent of genetic counselor (GC) engagement in variant interpretation in clinical practice is unknown. This study aimed to explore clinical GCs' variant interpretation practice across specialties, understand outcomes of this practice, and identify resource and educational needs., Methods: An online survey was administered to National Society of Genetic Counselors members providing clinical counseling., Results: Respondents (n = 239) represented all major clinical specialties. The majority (68%) reported reviewing evidence documented by the laboratory for most (>60%) variants reported; 45.5% report seeking additional evidence. Prenatal GCs were less likely to independently assess reported evidence. Most respondents (67%) report having reached a different conclusion about a variant's classification than the testing laboratory, though infrequently. Time was the most commonly reported barrier (72%) to performing variant interpretation, though the majority (97%) indicated that this practice had an important impact on patient care. When presented with three hypothetical scenarios, evidence typically used for variant interpretation was generally applied correctly., Conclusion: This study is the first to document variant interpretation practice broadly across clinical GC specialties. Our results suggest that variant interpretation should be considered a practice-based competency for GCs.

The purpose of this study was to determine if Eimeria oocysts recovered from litter at the time of chick placement in commercial broiler houses contained oocysts that were infectious for chickens. Over 100 litter samples were collected from 30 poultry farms representing a total of 60 different broiler houses with 9 houses sampled more than once over 1.5 yr. The samples were collected just before the placement of newly hatched chicks and after an anticoccidial drug (ACD) or Eimeria vaccine (VAC) program, and processed for counting oocysts followed by Eimeria species determination using ITS1 PCR. Broiler chicks were inoculated with recovered Eimeria oocysts to determine if the litter oocysts were viable and capable of causing patent infection. At placement, E. maxima (Emax) oocysts were detected in 70 of 75 houses after ACD program and 46 of 47 houses after VAC program. Eimeria acervulina, E. praecox, and/or E. tenella (Eapt) were detected in 75 of 75 houses after ACD program and 47 of 47 houses after VAC program. Viability testing revealed that 33.0% of broiler houses contained viable Emax oocysts, while 46.9% contained viable Eapt oocysts. During VAC programs, the concentration of Emax oocysts at placement and the total number of Emax oocysts shed by chickens in viability studies showed a very strong correlation (r = 0.83). Likewise, during ACD programs, the concentration of Eapt oocysts at placement and the total number of Eapt oocysts shed by chickens in the viability study showed a strong correlation (r = 0.62). In general, Eimeria oocyst levels at placement and number of viable oocysts shed by chickens in the viability study were similar among houses on the same farm. However, the number of Eimeria oocysts shed in the viability studies was considerably less than expected based on the number of oocysts given. These data suggest that nearly 100% of all poultry houses contain Emax and Eapt oocysts at placement with 30 to 50% of the houses containing viable Eimeria oocysts, thus possibly representing a source of the protozoa to newly hatched chicks., (© 2019 Poultry Science Association Inc.)

Background: The American Society for Clinical Pathology (ASCP) Board of Certification (BOC) surveys US certified cytotechnologists (CTs) at approximately 5-year intervals to gain information about current practice patterns. Although the purpose of this survey is to inform valid content development for the BOC CT examination, comparative longitudinal analysis of the survey data provides information about changes in cytotechnology practice., Materials and Methods: BOC Practice Analysis Survey data for 2009 and 2015 were examined, comparing survey demographics and performance of laboratory tasks. The 2015 survey added tasks not previously surveyed and considered them emerging when performed by a majority of respondents., Results: Two hundred thirty-five participants completed the survey in 2015 and 151 in 2009. Respondents reported an overall decrease in performing conventional Papanicolaou tests (-25.3%). Respondents reported increases in morphologic tasks such cytology-histology correlation (17.5%), cell-block interpretation (17.5%), and preliminary interpretation of histochemical stains (e.g., mucin and Grocott's methenamine silver stain) (16.7%), as well as quality assurance tasks. Majority-performed, newly surveyed tasks included touch prep preparation (57.8%) and interpretation (59.2%) and ancillary test triage (59.6%). Molecular tasks such as tumor identification (6.8%) and preparation of cytology specimens for oncology molecular testing (9.4%) did not meet majority-reporting thresholds., Conclusions: Although performance of the Papanicolaou test is declining, CTs report increases in additional morphologic as well as other laboratory tasks. Emerging tasks (2015) focus on FNA specimens. Knowledge of cytology practice patterns will help guide development of education and training resources toward maintaining an appropriately trained workforce., (Copyright © 2018 American Society of Cytopathology and the American Society of Clinical Pathology. All rights reserved.)

For piecewise constant magnetic fields, the Bloch equations (without relaxation terms) can be solved explicitly. This way the magnetization created by an excitation pulse can be written as a concatenation of rotations applied to the initial magnetization. For fixed gradient trajectories, the problem of finding parallel RF waveforms, which minimize the difference between achieved and desired magnetization on a number of voxels, can thus be represented as a finite-dimensional minimization problem. We use quaternion calculus to formulate this optimization problem in the magnitude least squares variant and specify first and second order derivatives of the objective function. We obtain a small tip angle approximation as first order Taylor development from the first order derivatives and also develop algorithms for first and second order derivatives for this small tip angle approximation. All algorithms are accompanied by precise floating point operation counts to assess and compare the computational efforts. We have implemented these algorithms as callback functions of an interior-point solver. We have applied this numerical optimization method to example problems from the literature and report key observations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC)., Patients and Methods: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic., Results: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable., Conclusions: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation., Trial Registration: ClinicalTrials.gov:NCT00789633., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

This case report describes the treatment and long-term follow-up care of a patient diagnosed with cleidocranial dysplasia who had multiple impacted permanent and supernumerary teeth. The aim of the treatment was to provide an adequate esthetic and functional reconstruction of the occlusion with good periodontal care. The patient was treated with a multidisciplinary therapeutic protocol including orthodontic and surgical procedures, and traction of 11 permanent teeth. The proposed objectives of good occlusion, normal function, healthy periodontium, and balanced profile were achieved, and the 3-year follow-up records showed stable results., (Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

The aim of this study was to establish an air-liquid interface (ALI) culture of precision-cut lung slices (PCLS) for direct exposure of lung cells to gaseous contaminants. Nitrogen dioxide (NO(2)) and ozone (O(3)) were selected as model gas compounds. Acute pro-inflammatory and toxic effects of NO(2) and O(3) on live lung tissue were investigated. Murine PCLS were exposed to different flow rates (3-30mL/min) of synthetic air, O(3) (3.5-8.5ppm), or NO(2) (1-80ppm). Tissue survived ex vivo in ALI culture and resisted exposure to NO(2) (1-10ppm) and O(3) (3.5-8.5ppm) for 1h. Longer exposure to NO(2) resulted in a clear loss of viability, whereas exposure to O(3) was less effective. Exposure to NO(2) dose-dependently induced release of the pro-inflammatory IL-1alpha (40%), whereas RANTES, IL-12, and eotaxin remained unchanged. Early secretion of IL-1alpha (80%), RANTES (>800%), MIP-1beta (44%), and MCP-1 (60%) was already detected after 1h of exposure to O(3). The obtained data showed that direct exposure to O(3) and NO(2) induced cytotoxicity and pro-inflammatory responses in PCLS with ALI culture. This provides a model that more closely resembles in vivo exposure of airborne contaminants, and thus should be appropriate for toxicity testing.

Uncovering the cis-regulatory logic of developmental enhancers is critical to understanding the role of non-coding DNA in development. However, it is cumbersome to identify functional motifs within enhancers, and thus few vertebrate enhancers have their core functional motifs revealed. Here we report a combined experimental and computational approach for discovering regulatory motifs in developmental enhancers. Making use of the zebrafish gene expression database, we computationally identified conserved non-coding elements (CNEs) likely to have a desired tissue-specificity based on the expression of nearby genes. Through a high throughput and robust enhancer assay, we tested the activity of approximately 100 such CNEs and efficiently uncovered developmental enhancers with desired spatial and temporal expression patterns in the zebrafish brain. Application of de novo motif prediction algorithms on a group of forebrain enhancers identified five top-ranked motifs, all of which were experimentally validated as critical for forebrain enhancer activity. These results demonstrate a systematic approach to discover important regulatory motifs in vertebrate developmental enhancers. Moreover, this dataset provides a useful resource for further dissection of vertebrate brain development and function., (Copyright 2009 Elsevier Inc. All rights reserved.)

Study Objectives: Patients who undergo surgical repair of thoracoabdominal aortic aneurysms have a high risk for the development of respiratory complications, which cause significant postoperative morbidity and prolong hospitalization, compared to patients who undergo other types of surgery. We studied whether prophylactic noninvasive application of nasal continuous positive airway pressure (nCPAP) administered via a facemask immediately after extubation may reduce pulmonary morbidity and shorten the length of hospitalization., Design: Prospective randomized clinical trial., Setting: Surgical ICU of a university hospital., Patients: Fifty-six patients following elective prosthetic replacement of the thoracoabdominal aorta, of whom 6 patients were excluded because they had received prolonged mechanical ventilation., Interventions: Following extubation in the ICU, nCPAP was applied for 12 to 24 h at an airway pressure of 10 cm H2O to patients in the study group (n = 25). Subjects in the control group (n = 25) received standard treatment including intermittent nCPAP (10 cm H2O for 10 min) every 4 h., Measurements and Results: In the study group, nCPAP was applied for a mean (+/- SD) duration of 23 +/- 3 h at an airway pressure of 10 +/- 1 cm H2O, which improved pulmonary oxygen transfer without altering hemodynamics (ie, heart rate, mean arterial BP, and central venous pressure). The application of nCPAP was associated with fewer pulmonary complications (Pa(O2)/fraction of inspired oxygen [F(IO2)] <100, atelectasis, pneumonia, reintubation rate) compared to the control group (7 of 25 patients vs 24 of 25 subjects, respectively; p = 0.019). The mean duration of intensive care treatment tended to be shorter in the study group compared to the control group (8 +/- 1 vs 12 +/- 2 days, respectively; difference not significant), while the mean length of hospital stay was shorter with nCPAP therapy (22 +/- 2 vs 34 +/- 5 days, respectively; p = 0.048)., Conclusions: The prophylactic application of nCPAP at airway pressures of 10 cm H2O significantly reduced pulmonary morbidity and length of hospital stay following the surgical repair of thoracoabdominal aortic aneurysms. Thus, it can be recommended as a standard treatment procedure for this patient group.

The in vitro study of adverse cellular effects induced by inhaled pollutants poses a special problem due to the difficulties of exposing cultured cells of the respiratory tract directly to test atmospheres that can include complex gaseous and particulate mixtures. In general, there is no widely accepted in vitro exposure system. However, in vitro methods offer the unique possibility for use of human cells, developed and validated cell culture and exposure device (CULTEX(1)) using the principle of the air/liquid exposure technique. Cells of the respiratory tract are grown on porous membranes in transwell inserts. After removal of the medium, the cells can be treated on their superficial surfaces with the test atmosphere, and at the same time they are supplied with nutrients through the membrane below. In comparison with other experimental approaches, the goal of our studies is to analyze the biological effects of test atmospheres under environmental conditions, i.e. without humidifying the atmosphere or adding additional CO(2). The system used is small and flexible enough independent of a cultivation chamber and thus offers the opportunity for onsite study of indoor and outdoor atmospheres in the field. The efficacy of the exposure device has already been demonstrated in the analysis of dose-dependent cytotoxic and genotoxic effects of exposure of epithelial lung cells to complex mixtures such as native diesel exhaust and side-stream smoke.

The advent of microarray technology, coupled with the availability of mouse cDNA collections derived specifically from preimplantation embryos, helps to provide global gene expression profiles for the earliest stages of development. However, to determine the functions of the large numbers of genes of interest, massive systematic functional assays such as gene 'knockdown' experiments are required. As a first step, the relative suppression of blastocyst formation by differentially-modified antisense oligonucleotides to E-cadherin was assayed. The injection of 2'-methoxyethoxy (2'-MOE)-modified oligonucleotides blocked the formation of blastocysts in two-thirds of embryos, whereas the injection of either control missense 2'-MOE-oligonucleotides, or oligonucleotides with a Morpholino modification, had no significant effect on embryonic development. Thus, the 2'-MOE-modified antisense oligonucleotides are candidates for effective examination of roles of large numbers of genes during early embryological development.

An experimental in vitro model was established to study the effects of environmentally relevant gaseous compounds on lung cells. The technical unit consists of a gas reaction chamber (2400 l) with a sun-simulator to produce and photochemically transform gaseous mixtures and compounds at the upper limit of environmentally relevant concentrations. Rat lung cells were exposed on transwells in a perspex chamber inside an incubator, into which the gaseous mixtures were conducted. Analysis of the gas phase was performed inside the reaction chamber and at the outlet of the exposure box to assess the effective exposure concentrations. The growth of the cells on PET-membranes allowed direct cell exposure with a minimal barrier for contact between gas and cells. To assess the cytotoxicity, the following biochemical markers for the cellular status after exposure were determined: amount of dsDNA, WST, BrdU-incorporation after exposure, LDH release into the culture medium, activity of glutathione S-transferases and esterases. Using this system, dose-dependent cytotoxicity was found for NO2 in the concentration range from 80 to 360 ppb and strong cytotoxic effects for ozone in the concentration range from 225 to 500 ppb. Exposure to purified air did not show significant effects. In addition, some irradiated gas mixtures (photo smog) showed cytotoxicity whereas non-irradiated mixtures did not.

Study Objective: To evaluate the effects of oral, intramuscular (i.m.) and intravenous (i.v. glycopyrrolate on oral and gastric secretions, and to assess how these routes of administration change intubating conditions., Design: Randomized, double-blinded study., Setting: University hospital operating room., Patients: 37 ASA status I and II general anesthesia patients., Interventions: Patients were randomized to receive glycopyrrolate or placebo just before surgery by three routes: oral, i.m., and i.v.. Glycopyrrolate was received once by one route and placebo by the other two routes. A placebo group received three placebos and no glycopyrrolate., Measurements and Main Results: Mouth conditions and intubating conditions were qualitatively assessed by the patient and the intubating anesthesiologist. No difference between groups was noted. Oral and gastric volumes were measured and showed significantly less gastric volume for the i.v. group as compared with the other groups. Oral secretions were reduced in both the i.v. and i.m. groups when compared with placebo or glycopyrrolate administered orally., Conclusions: Preoperative glycopyrrolate is significantly more effective at reducing oral and gastric secretions if administered intravenously immediately before induction.

The cellular distribution of guanylyl cyclase coupled natriuretic peptide receptors type A (GC-A) and type B (GC-B) was examined by immunocytochemistry in normal rat kidney, and compared with the distribution of the vacuolar H(+)-ATPase. Staining for GC-A was found in glomeruli, thin limbs of Henle's loop, cortical collecting tubule, and inner medullary collecting duct. Staining for GC-B was found in glomeruli and the same nephron sections as GC-A, with the exception of the thin limbs. In the cortical collecting tubule, GC-A was found in both principal and intercalated cells; GC-B was restricted to the apical pole of alpha intercalated cells. In inner medullary collecting duct cells, GC-A was located on the basal membrane, whereas GC-B was found in the apical pole. The different pattern of polarization of natriuretic peptide receptors in the inner medulla provides a plausible basis for the different physiologic effects of atrial natriuretic factor and C-type natriuretic peptide. The results also suggest the possibility that GC-B is involved in the regulation of bicarbonate transport in the cortical collecting tubule.

Atriopeptin (AP) is synthesized and stored in the mammalian atria as a 126 amino acid prohormone (AP126). Upon secretion, the prohormone undergoes site specific proteolysis within the atria to yield the carboxyl terminal 28 amino acid hormone (AP28). The atrial cell responsible for AP126 bioactivation has not yet been determined. Primary neonatal rat atrial cell cultures were generated with and without depletion of nonmyocytic cells. The molecular form of AP detected in the conditioned media of mixed cultures was determined to be AP126. Addition of dexamethasone to these cultures resulted in the appearance of a peptide that co-migrated with AP28. In contrast, no AP126 processing was detected in the conditioned media of myocyte enriched cultures when grown in the presence of dexamethasone. Readdition of nonmyocytic atrial cells to myocyte enriched cultures successfully reconstituted the steroid induced AP126 processing. Incubation of recombinant AP126argarg with nonmyocytic atrial cell cultures resulted in the generation of AP28argarg. We conclude that a nonmyocytic atrial cell is responsible for AP126 processing in vitro.

From 1975 through 1982, the Damus-Stansel-Kaye procedure was performed on 20 patients with complete transposition of the great arteries (TGA) and on 4 with double-outlet right ventricle (DORV) and subpulmonary ventricular septal defect (VSD). The patients ranged from 6 days to 20 years old (median age, 13 months). Associated anomalies included atrial septal defect (24 patients), VSD (14), and others (25). Thirteen patients had had palliative operations previously. Of the 14 hospital deaths (58%), 13 occurred among the 17 patients with one or more risk factors: age less than 18 months, weight less than 10 kg, and left ventricular peak systolic pressure less than 75% of systemic pressure. Follow-up ranged from 12 to 87 months (mean, 51 months). One patient died of cardiac failure two years postoperatively, and 2 required conduit replacement at 40 and 50 months because of stenosis. All 9 survivors are free from major symptoms. The Damus-Stansel-Kaye repair is most suitable for patients with TGA or DORV with subpulmonary VSD who are older than 18 months, weight more than 10 kg, and have a "prepared left ventricle," and whose coronary artery anatomy precludes transplantation.

The development of an accurate method for the detection and typing of genital human papillomavirus is of substantial clinical importance. This virus has been implicated as an etiologic agent in the development of cervical neoplasia. To detect human papillomavirus infection with maximum sensitivity, cells must be collected and assayed for human papillomavirus deoxyribonucleic acid. We compared two noninvasive methods of sampling exfoliated cervical cells--cervicovaginal lavage and scrape-Cytobrush. Seventy-four patients newly referred to the colposcopy clinic were divided randomly for cell sampling by either cervicovaginal lavage followed by scrape-Cytobrush or, conversely, scrape-Cytobrush followed by cervicovaginal lavage. Restriction analysis and Southern blot hybridization were used to test all the samples thus obtained for human papillomavirus. Overall, test results from 42 patients (56.8%) were positive for human papillomavirus deoxyribonucleic acid. Twenty-six (31.1%) tested positive for human papillomavirus by both sampling methods, and 32 (43.2%) tested negative for human papillomavirus by both methods. One (1.4%) tested positive with scrape-Cytobrush sampling but negative with cervicovaginal lavage, while 15 (20.3%) tested negative with scrape-Cytobrush but positive with cervicovaginal lavage (p less than 0.001, McNemar's test). These data, combined with previous work from our group, suggest that, of the available methods, cervicovaginal lavage, coupled with human papillomavirus deoxyribonucleic acid hybridization, is the most sensitive noninvasive method for harvesting cells for molecular identification of human papillomavirus in the female lower genital tract.

In 1983, a comprehensive programme was introduced to halt the spread of hepatitis B virus (HBV) infection and to reduce mortality from hepatocellular carcinoma (HCC) in Alaskan Natives, in whom the incidence of HBV infection was high. This programme includes: serological screening of all Alaskan Natives; immunisation of susceptible persons, including all newborn babies, with hepatitis B vaccine; and testing HBsAg-positive carriers twice a year for alpha-fetoprotein (AFP) to detect HCC at an early stage. By October, 1986, over 53,000 Alaskan Natives (84% of the total Native population) had been tested for HBV serological markers and 80% of the identified susceptibles had been or were being vaccinated against HBV. After complete immunisation of 90% of the susceptibles in the area with the highest infection rates in Alaska, the annual incidence of acute symptomatic HBV infection decreased from 215 to 14 cases per 100,000 population. After the introduction of AFP screening, the 1-year-case-fatality rate for HCC fell, from 100%, to 50%.

Clinical, catheterization, and pathologic findings were recorded in a newborn infant with tuberous sclerosis and multiple cardiac rhabdomyomas that produced a clinical picture simulating mitral atresia and the hypoplastic left-heart syndrome. The clinical picture was due to a left atrial tumor that completely obstructed the mitral valvular orifice. Even if the diagnosis of left atrial tumor had been made, successful surgical correction was unlikely because of left ventricular rhabdomyomas, which produced severe subvalvular aortic stenosis and did not appear to be resectable. This case demonstrates the possibility that a hamartoma, such as a rhabdomyoma, occasionally can mimic the hypoplastic left-heart syndrome.

Specific types of human papillomavirus are currently implicated as etiologic agents of precancerous and cancerous lesions of the cervix. We have previously described the use of cervicovaginal lavage and molecular hybridization to detect human papillomavirus infections of the cervix. We report here the predictive value of this method of human papillomavirus detection to identify women with biopsy proved dysplastic and cancerous lesions of the cervix. One hundred ninety-one women from a city hospital colposcopy clinic underwent concurrent Papanicolaou smear, cervicovaginal lavage, and coloposcopically directed cervical biopsy. Human papillomavirus deoxyribonucleic acid was detected in 114 (59.7%) of these women. Of the positive results, human papillomavirus type 16 accounted for 23.7%, human papillomavirus type 18 for 10.5%, human papillomavirus type six or 11 for 6.2%, related human papillomavirus types for 52.6%, and 7.0% contained more than one type. The distribution of human papillomavirus types was similar in both women younger than 40 years of age and in older women. Eighty-nine of 128 (69.5%) women less than 40 years old with cervical lesions had positive findings of human papillomavirus, and 18 of 29 (62.1%) older women with cervical lesions had positive findings of human papillomavirus. Detection of human papillomavirus types 16 and 18 identified only 35 of 157 (22.3%) women with cervical lesions. The sensitivity of detecting all types of human papillomavirus as a predictor of a biopsy proved lesion (68.0%) was comparable with the sensitivity of cytologic examination alone (74.0%). However, human papillomavirus detection combined with the Papanicolaou smear provided an increased overall sensitivity of 89.3% (p less than 0.01). In fact, women either positive for human papillomavirus or having abnormal cytologic findings were 11.8 times more likely to have a biopsy proved cervical lesion than human papillomavirus-negative women with negative cytologic results (95% confidence interval for odds ratio: 5.3 to 26.6). We conclude that the sensitivity of cytologic examination plus human papillomavirus detection is superior to the use of either cytologic studies or human papillomavirus detection alone in identifying patients with cervical lesions.

Miniature swine were fed brominated sesame oil at dietary levels of 0, 5, 25, 50 or 500 mg/kg of body weight for 17 weeks and brominated soybean oil at levels of 0, 5, 50 or 500 mg/kg of body weight for 28 weeks. Growth rate and food intake were decreased only at the high dose level in the brominated sesame oil study. In both studies, signs of lethargy and ataxia occurred in pigs fed the highest dose, and were probably due to a dose-related increase in serum bromine concentrations. Marked elevations in lactic dehydrogenase (LDH), serum glutamic-oxalacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) values were seen at the highest dose level with both substances and these enzyme activities were increased at the 50 mg/kg dose level in the brominated sesame oil study. Histopathologic lesions were confined to animals given the highest dose level of either oil. Marked fatty degeneration of the hepatic plate cells and renal tubular epithelial cells were seen in both studies. In the brominated sesame oil study, neutral fat was moderately increased in the myocardium of the pigs fed 500 mg/kg. However, marked diffuse accumulation of LDH, marked diffuse fatty degeneration and focal degeneration, and/or necrosis of individual or small groups of cardiac muscle fibers were seen in the group fed brominated soybean oil at 500 mg/kg. A moderate to marked testicular atrophy was also observed in this group. A dose-related accumulation of total and hexane-soluble bromine was observed in all tissues examined in both studies; the highest concentrations occurred in adipose tissue of the pigs given the highest dose level. Kidneys, livers, hearts and thyroids of these groups also contained large amounts of bromine. In pigs given the 50 mg/kg dose level, total and hexane-soluble bromine concentrations were higher in the brominated sesame oil study than in the longer brominated soybean oil study and may be responsible for the elevations in LDH, SGPT and SGOT activities in this group.

Human papillomavirus infection is implicated as an etiologic agent in the development of neoplasia and invasive carcinoma of the cervix. To detect human papillomavirus infection of the cervix, cells must be collected and assayed for human papillomavirus-related deoxyribonucleic acid sequences. Gynecologists and other clinical investigators generally use an exocervical spatula scrape and an endocervical swab for cell collection, analogous to Papanicolaou smear collection. However, inadequate cell recovery is common. To overcome this problem, we have developed the cervicovaginal lavage method for human papillomavirus detection. In the present study we compared the cervicovaginal lavage method with the widely used scrape-swab method in 48 women referred for colposcopic examination. After a Papanicolaou test, two samples were obtained from each woman, either with cervicovaginal lavage followed by scrape-swab or with the scrape-swab followed by cervicovaginal lavage. Human papillomavirus types were assessed by restriction analysis and Southern blot hybridization. In 21 women (44%) test results were positive for human papillomavirus with both the scrape-swab and cervicovaginal lavage cell collection methods; in nine women (19%) test results were positive only with the cervicovaginal lavage method; and in 18 women (38%) results were negative for human papillomavirus with both techniques. None of the women had human papillomavirus detected by scrape-swab without also having it detected with cervicovaginal lavage. The human papillomavirus deoxyribonucleic acid types identified were concordant in the 21 women whose infections were detected with both sampling methods, although the second virus type was detected only with cervicovaginal lavage in one woman who had a mixed genital tract infection. We concluded that cervicovaginal lavage is a more sensitive cell collection method than the scrape-swab technique for assessing human papillomavirus infection of the cervix.

Straddling atrioventricular valve (SAVV) is a rare anomaly. Only recently have the premortem diagnostic features been elucidated. Repair of the associated ventricular septal defect poses a considerable technical problem. Corrective operations, infrequently reported, have usually involved replacement of the SAVV. This report describes the successful management of a patient with a straddling left atrioventricular valve in whom the valve was preserved by a technique previously used for septation of the univentricular heart. This technique offers a useful alternative to valve replacement in the management of patients with SAVV.