Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection

Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome aberrations including two cases of 47,XXY, four cases involving a 45,X cell line and three autosomal trisomies. Molecular analysis of the parental origin of the deleted or supernumerary chromosome was performed by using polymorphic microsatellite markers. Six cases involving a sex chromosome abnormality were found to be of paternal origin while the two trisomic cases that could be analysed were of maternal origin. Two cases involved the same infertile couple who had two consecutive ICSI pregnancies terminated because of a chromosome abnormality. The replaced embryos in both cases originated from a single batch of ICSI fertilized oocytes of which part was used to initiate the first pregnancy and part was cryopreserved and used to initiate the second pregnancy.      

Further investigation of the association between gastroesophageal reflux and bronchoconstriction

A double-blind modification of the intraesophageal acid perfusion challenge (Bernstein procedure) was performed in asthmatic subjects with and without gastroesophageal reflux, nonasthmatic subjects with reflux, and normal subjects. Conventional spirometric functions and total respiratory resistance (Rrs) were measured prior to and after the infusion. There were no changes in pulmonary functions except in the asthmatic subjects who had had a positive add challenge. The greatest changes occurred in Rrs, which increased significantly with reflux symptoms (p < 0.01) and decreased toward baseline (p < 0.05) when these symptoms were relieved with antacids. The response was even greater in asthmatic subjects who associated reflux symptoms with attacks of asthma. These results support previous findings that acid reflux symptoms could cause a bronchoconstrictive response in certain asthmatic patients.     

Analysis of myocilin mutations in 1703 glaucoma patients from five different populations

A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.     

Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in- vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.      

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Severe Acute Respiratory Syndrome Coronavirus 2 Seropositivity among Healthcare Personnel in Hospitals and Nursing Homes,Rhode Island,USA, July–August 2020

Healthcare personnel are recognized to be at higher risk for infection with severe acute respiratory syndrome coronavirus 2. We conducted a serologic survey in 15 hospitals and 56 nursing homes across Rhode Island, USA, during July 17–August 28, 2020. Overall seropositivity among 9,863 healthcare personnel was 4.6% (95% CI 4.2%–5.0%) but varied 4-fold between hospital personnel (3.1%, 95% CI 2.7%–3.5%) and nursing home personnel (13.1%, 95% CI 11.5%–14.9%). Within nursing homes, prevalence was highest among personnel working in coronavirus disease units (24.1%; 95% CI 20.6%–27.8%). Adjusted analysis showed that in hospitals, nurses and receptionists/medical assistants had a higher likelihood of seropositivity than physicians. In nursing homes, nursing assistants and social workers/case managers had higher likelihoods of seropositivity than occupational/physical/speech therapists. Nursing home personnel in all occupations had elevated seropositivity compared with hospital counterparts. Additional mitigation strategies are needed to protect nursing home personnel from infection, regardless of occupation.     

Comparison of ejection fraction and Goldman risk factor analysis to dipyridamole-thallium 201 studies in the evaluation of cardiac morbidity after aortic aneurysm surgery

Associated coronary artery disease is the critical factor that influences early and late mortality after abdominal aortic aneurysm surgery. Dipyridamole-thallium 201 scintigraphy, left ventricular ejection fraction, and Goldman risk factor analysis have been suggested as preoperative noninvasive screening methods to detect significant coronary artery disease. In this series of 95 elective abdominal aortic aneurysm repairs dipyridamole-thallium 201 scintigraphy was highly predictive of the absence of perioperative cardiac morbidity (96% specificity, 44/46 normal scans, no cardiac morbidity), whereas ejection fraction (73% specificity, 31/42 normal ejection fraction, no cardiac morbidity) and Goldman risk factor analysis (84% specificity, 44/51 class I, no cardiac morbidity) were less. Furthermore, thallium redistribution on dipyridamole-thallium 201 scintigraphy leading to coronary angiography identified a significant number of patients with occult coronary artery disease who required preoperative coronary revascularization (8%, 8/95) and might have remained undetected on the basis of left ventricular ejection fraction or Goldman risk factor analysis. Finally, fixed thallium deficit, which some investigators have interpreted as a low probability finding for cardiac morbidity, was associated with a higher than expected incidence of cardiac complications. Forty-six percent (7/15) of all postoperative cardiac complications (three myocardial infarctions, three ischemic events, one death) occurred in patients with abdominal aortic aneurysms with fixed deficits. This suggests that patients with fixed deficits on dipyridamole-thallium 201 scintigraphy should be considered for later "delayed" (4 hours) thallium images or coronary angiography or both.     

Analysis of human cancer DNA's for DNA sequence of human adenovirus serotypes 3, 7, 11, 14, 16, and 21 in group B1

We have investigated whether Group B human adenoviruses (Ad) (Ad3, Ad7, Ad11, Ad14, Ad16, and Ad21), which are widespread in the human population and are tumorigenic in hamsters, may play a role in human cancer. Hybridization of Ad7-radiolabeled DNA with DNA's from an Ad7-induced primary hamster tumor and from two cell lines (5728 and Ad7 P-cell) established from Ad7-induced hamster tumors indicated multiple copies per cell of 17, 30 to 36, and 20%, respectively of the Ad7 genome. Thus, cells transformed by Group B Ads resemble cells transformed by Group C and Group A Ad's in that they retain multiple copies of a variable fraction of the viral genome. These model studies suggest that possible Group B Ad-induced human cancer cells should contain one or more copies of virus DNA per cell. Therefore, we assayed human cancer DNA's for Ad sequences, by highly sensitive "saturation-hybridization" reactions with Ad7 or Ad11 DNA (4 X 10(6) to 2.1 x 10(8) cpm/microgram). We concentrated on cancers of the respiratory and digestive systems, because these systems are the most common sites of infection by Group B Ad's. In 8 independent experiments, no Ad7 sequences were detected in DNA's from 16 normal lung tissues, 18 normal tissues of the digestive system, 34 cancers of the respiratory system, 19 cancers of the digestive system, 11 cancers of the urinary system, 5 cancers of the genital system, 3 cancers of the breast, and 6 Hodgkin's lymphomas. Reconstruction controls with added Ad7 DNA indicated that about 0.05 to 0.1 copy of Ad7 DNA per cell should be detected. Ad11 is strongly implicated as a cause of acute hemorrhagic cystitis. In two independent experiments, no Ad11 sequences were detected in DNA's from 9 carcinomas of bladder, 10 carcinomas of prostate, 24 carcinomas of kidney, 3 hypernephromas, 3 Wilms' tumors, or 2 normal kidneys. Reconstruction experiments indicated that the cancer DNA assays had a sensitivity of 0.05 to 0.1 copy of Ad11 DNA per cell. The DNA's of Group B Ad's are greater than 85% homologous by hybridization; thus, these results are applicable to all Group B serotypes. Our data provide evidence (but not formal proof) that none of the human cancers that we analyzed were induced by Group B Ad's. These tumors represent about 50% of the tumors that affect humans. The possible involvement of Group B Ad's in other less common forms of human cancers is under investigation in our laboratory.     

Impact of providing audiotapes of primary adjuvant treatment consultations to women with breast cancer: a multisite, randomized, controlled trial.

PURPOSE: Women with breast cancer were provided with an audiotape of their primary adjuvant treatment consultation, and the following patient outcomes were measured at 12 weeks postconsultation: perceived degree of information provision, audiotape satisfaction and use, communication satisfaction with oncologist, mood state, and cancer-specific quality of life. PATIENTS AND METHODS: Participants included 628 women newly diagnosed with breast cancer and 40 oncologists from six cancer centers in Canada. The patients were block randomized to one of four consultation groups: standard care control, not audiotaped; audiotaped, no audiotape given; audiotaped, patient given audiotape; and audiotaped, patient offered choice of receiving audiotape or not. RESULTS: Patients receiving the consultation audiotape had significantly better recall of having discussed side effects of treatment than patients who did not receive the audiotape. Audiotape benefit was not significantly related to patient satisfaction with communication, mood state, or quality of life at 12 weeks postconsultation, and was not significantly affected by choice of receiving the audiotape. Patients rated the audiotape intervention positively, with an average score of 83.9 of 100. CONCLUSION: Audiotape provision benefits patients by facilitating their perception of being informed about treatment side effects, but does not significantly influence patient satisfaction with communication, mood state, or quality of life.