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Fragile X syndrome (FXS) is the leading single-gene cause of inherited intellectual disability and autism [...]

Objectives Based on the reported success of stereotactic body radiotherapy in treating extracranial tumors, we used CyberKnife (Accuray Incorporated, Sunnyvale, CA) to treat patients with metastatic lung cancer. Methods This is a retrospective report of treatment details and outcomes of 35 patients, ranging in age from 33 to 91 years, with 69 histologically proven pulmonary metastases, treated by image-guided robotic stereotactic radiosurgery at the CyberKnife Center of Miami, between March 2004 and August 2007. Tumor volumes ranged from 0.7 mL to 152 mL. Total doses ranged from 5 to 60 Gy delivered in one to four fractions with an equivalent dose range from 6 to 110 Gy NTD delivered in 2-Gy fractions assuming an alpha/beta of 20 Gy. Results All patients tolerated radiosurgery well with fatigue as the main side effect. Grade 3 and grade 4 pulmonary toxic reactions were observed in one patient who had undergone a repeat treatment. Of the 35 treated patients, 27 (77%) were still alive at a median 18-month (range 2-41 mo) follow-up. Local control was 71% with 25 tumors showing a complete response, 16 a partial response, and 7 stable with disease. Eight had progressive disease. Conclusions The delivery of precisely targeted radiation doses to lung tumors in a hypofractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery of pulmonary metastases with the CyberKnife achieves good rates of local disease control with limited toxicity to surrounding tissues and in many cases may be beneficial for patients for whom surgery is not an option.

This study investigated the relationship between the Future Temporal Orientation (FTO) and academic performance of African American high school students. We hypothesized that the relationship between FTO and academic performance would be mediated by students’ perceptions of the usefulness of an education and their valuing of academic work and that the relationships between FTO and the hypothesized mediators would be moderated by students’ perceptions of school and societal inequity. The students (N = 334) completed questionnaires assessing their temporal orientation and educational attitudes, and GPAs were gathered from their transcripts. Results and post hoc analyses supported the existence of a three-step process: FTO was associated with perceptions of education usefulness, which was then associated with valuing academic work (a relationship moderated by perceived unfair treatment at school), which was then associated with GPAs. The significance of FTO development as a normative process and possible protective factor against depressed academic achievement are discussed.

Problem We have previously determined that long non-coding RNAs (lncRNAs) are differentially expressed in preterm premature rupture of membranes (PPROM) and hypothesized that the collagenolysis ubiquitin–proteasome system may be activated by infection and inflammation. However, direct evidence of the involvement of lncRNAs in transcriptional and posttranscriptional regulation of the infection-triggered alteration of collagen is lacking. Method of study A previously developed mouse model with MHV68 viral infection was assessed to determine whether viral infection may induce differential expression of lncRNAs in mouse placentas and amniotic sacs. Results Differential expression of lncRNAs that are associated with collagen was found in HMV68 viral-infected, compared to non-infected, mouse placentas and amniotic sacs. Differential expression of messenger RNAs (mRNAs) of collagen was also documented. Conclusions Our data demonstrate, for the first time, that viral infection may induce the differential expression of lncRNAs that are associated with collagen. Based on this finding, we propose that lncRNA may have involved in regulating of infection-induced collagen transcription.

Background Health care is being changed dramatically by the marriage of computers and telecommunications. Implications for hospitals and physicians already have received extensive media attention, but comparatively little has been said about the impact of information technology on dentistry. This article illustrates how the digital transformation will likely affect dentists and their patients. Conclusions Based on recent experiences of hospitals and medical practices, dentists can expect to encounter revolutionary changes as a result of the digital transformation. The Internet, the World Wide Web and other developments of the information revolution will redefine patient care, referral relationships, practice management, quality, professional organizations and competition. Practice Implications To respond proactively to the digital transformation of oral health care, dentists must become familiar with its technologies and concepts. They must learn what new information technology can do for them and their patients and then develop creative applications that promote the profession and their approaches to care.

This article describes the techniques for performing a video-assisted thoracic surgery (VATS) lobectomy. Each lobe can be approached from anteriorly, posteriorly, or intralobarly. Each method is described and the advantages of each technique are discussed. The surgical results in 105 cases are presented. The VATS technique has decreased operative trauma and has shortened hospital stay with a concomitant reduction in cost to the patient and health-care provider. These advantages make VATS lobectomy an excellent alternative for excision of well localized peripheral lung cancer.

Academic administrators rely on archival records for a variety of administrative, legal, financial, and historical reasons. In fact, the primary mission of many college and university archives is to manage these non-current records. In an era of increasing fiscal constraint and limited resources, accurate analysis of the use of archival information by university administrators is crucial to the development of successful, responsive archival programs. The authors believe the administrative use of archival records is an understudied aspect of archival administration. This study examines the information environment on modern campuses, explores the evolving roles of traditional and emerging information sites, examines the information use patterns of academic administrators, and proposes methods for improved information service in the modern academic environment.

Metastatic malignant melanoma is an incurable disease with a median survival of 8.5 months and a probability of surviving five years after the diagnosis of less than 5%. To date, no systemic therapy has meaningfully changed these survival end points. A case of metastatic melanoma treated with combined modalities including image-guided robotic radiosurgery with CyberKnife® (Accuray Incorporated, Sunnyvale, CA, USA), and has an overall survival of 14 years is presented.

To determine whether robotic stereotactic radiotherapy of 70-75 Gy delivered in five fractions results in an improved therapeutic ratio, compared with three fractions, in the treatment of peripheral non-small-cell lung cancer (NSCLC), in which case doses of up to 85 Gy in five fractions may be feasible.Between December 2006 and May 2010, 20 patients (9 female, 11 male, aged 65 to 88) were treated using the CyberKnife® Robotic Radiosurgery System for NSCLC with doses ranging from 67 Gy to 75 Gy based on location, histopathological type, grade of histopathological differentiation, tumor diameter/volume, and normal tissue constraints, with the doses being delivered in five fractions over 5 to 8 days. Tumor diameters ranged from 1.5 cm to 3.4 cm (median: 2.5 cm). Patients with Stage I to IV NSCLC were treated, and the results and observations were analyzed for clinical characteristics and outcomes including toxicity. All patients, except one who had refused surgery, had co-morbid conditions that precluded a lobectomy.Twenty patients were followed every three months by positron emission tomography/computed tomography (PET/CT). Mean follow-up was 23 months (range: four to 58 months). Local control was achieved in all treated tumors. Three patients expired, and three developed new regional metastases, none of which was within the planning target volume (PTV). The remainder of the patients demonstrated no evidence of recurrence or continued growth detectable by PET/CT. There was no toxicity above Grade 1.It is feasible to treat peripheral NSCLC with individualized maximal tolerable doses ranging from 67 Gy to 75 Gy in five fractions chosen on the basis of location, histopathological type, grade of histopathological differentiation, tumor diameter/volume, and normal tissue constraints.

Aims To determine the effectiveness of robotic stereotactic radiotherapy with image guidance and real-time respiratory tracking against early stage peripheral lung cancer. Materials and methods We treated patients with stage I non-small cell lung cancer (NSCLC) with CyberKnife ® and analysed their clinical characteristics and outcomes. All patients had co-morbid conditions that precluded lobectomy. The clinical target volume (CTV) included the gross tumour volume (GTV) and a 6mm margin in all directions to account for microscopic extension. The planning target volume (PTV) equalled CTV+2mm in all directions for uncertainty. Tumour motion was tracked using a combination of Synchrony ® and Xsight ® Spine tracking methods with the aid of a single gold marker implanted in the centre of the tumour, or using the newer Xsight ® Lung method without markers for selected tumours. A 60–67.5Gy dose was prescribed to the 60–80% isodose line (median 65%) and given in three to five fractions. Patients were followed every 3 months for a median of 27.5 months (range 24–53 months). Results Of the 67 patients with NSCLC stage IA or IB treated between January 2004 and December 2008, we report the results of a cohort of 31 with peripheral stage I tumours of 0.6–71cm 3 volume treated between January 2004 and December 2007 with total doses between 60 and 67.5Gy in three to five fractions. The median D max was 88.2Gy and the median V 95 of the PTV was 99.6% or 27.9cm 3 . No grade 3 or above toxicity was encountered. Four cases of radiation pneumonitis and one case of oesophagitis were observed. In those patients whose pre- and post-treatment results were available, no change in pulmonary function tests was observed. Actuarial local control was 93.2% for 1 year and 85.8% for up to 4.5 years. One-year overall survival was 93.6% and 83.5% for up to 4.5 years, as projected by Kaplan–Meier analyses. Conclusions In this small cohort of patients with stage I peripheral NSCLC, robotic stereotactic radiotherapy seems to be a safe and obviously superior alternative to conventionally fractionated radiotherapy, with results that may be approaching those obtained with lobectomy without the associated morbidity.

To determine if image-guided robotic stereotactic radiosurgery (IGR-SRS) by CyberKnife achieves acceptable local control in resectable but medically inoperable patients with non-small cell lung cancer (NSCLC) or pulmonary metastasis, and to evaluate control rates and toxicity.Treatment details and outcomes were reviewed for 95 patients (age range 33-96 years) with 136 histologically proven cancers treated by IGR-SRS at the CyberKnife Center of Miami between March 2004 and March 2007. Tumor volumes ranged from 1.2 cc to 338 cc. Targeting was accomplished using combined skeletal alignment and real-time tracking via fiducials placed within the tumor. Total doses ranged from 15 to 67.5 Gy delivered in 1 to 5 fractions.Of the 95 patients treated, 78 (82%) are still alive at 1 to 36 months post-treatment. Nineteen patients have died, four from disease other than cancer progression. All patients but one achieved at least partial response to treatment and tolerated radiosurgery well. For the majority of our patients, fatigue had been the main side effect.The delivery of precisely targeted high radiation doses with surgical precision to lung tumors in a hypo-fractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery (IGR-SRS) of lung tumors with the CyberKnife achieves excellent rates of local disease control with limited toxicity to surrounding tissues, and in many cases may be curative for patients for whom surgery is not an option.

PURPOSE The aims of this study were to determine if image-guided robotic stereotactic radiosurgery by CyberKnife® Radiosurgery System using ablative radiation doses achieves acceptable local control in medically inoperable patients with early non–small-cell lung cancer (NSCLC) and to evaluate disease-free survival, toxicity, and failure. CyberKnife® can deliver the prescribed dose by using many different angles converging on the target, with real-time target tracking through a combined orthogonal radiograph imaging and optic motion tracking system (Synchrony®). MATERIALS AND METHODS A review of treatment details and outcomes for 59 patients, ranging in age from 51 years to 96 years, with 61 tumors with histologically proven cancers treated by image-guided robotic stereotactic radiosurgery at the CyberKnife Center of Miami between March 2004 and March 2007 is presented. Target localization and respiratory movement compensation were accomplished using a single fiducial marker placed within the tumor, and the X-Sight TM and Synchrony® systems. Total doses ranged from 15 Gy to 67.5 Gy delivered in 1-5 fractions with an equivalent dose range of 24-110 Gy normalized treatment dose in 2 Gy fractions (α/β = 20 Gy). RESULTS Four patients with stage 1A NSCLC and 2 patients with stage 1B NSCLC had persistent or recurrent disease. All patients tolerated the radiosurgery well, fatigue being the main side effect. Of the 59 patients treated, 51 (86%) were still alive at 1-33–month follow-up. Eight patients have died, 2 of diseases other than cancer progression. CONCLUSION The results indicate that the delivery of precisely targeted ablative radiation doses with surgical precision to limited treatment volumes of lung tumors in a hypofractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery of lung tumors with CyberKnife® achieves excellent rates of local disease control with limited toxicity to surrounding tissues and, in many cases, might be curative for patients for whom surgery is not an option.

Stereotactic body radiosurgery (SBRS) of lung tumors with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) achieves excellent rates of local disease control with limited toxicity to surrounding tissues. We retrospectively reviewed treatments and outcomes for 90 patients with 109 lung lesions treated at the CyberKnife Center of Miami between March 2004 and September 2006. This monotherapy review included 49 patients with 53 primary lung cancers, 27 patients with 42 pulmonary metastases, 6 patients with external beam failure and 8 patients treated by SBRS as a boost following or before conventionally fractionated radiotherapy (3DCRT or IMRT). In the primary tumor category, 43 patients remain alive. Thirty-two have been followed 1 to 25 months (median = 11.5 months). Fortynine percent (21/43) of them have had a complete radiographic response and have been followed for a median of 18.5 months. Another 8 have evidence of at least a partial radiographic response. There have been 5 failures (5/43) within the PTV, for a local recurrence rate of 11%. Of the total 109 treated lesions, 97/109 (89%) showed radiographic evidence of at least a partial response to treatment. Six of the failures were in lesions 100 cc. All of the patients tolerated SBRS well with fatigue as the main toxicity. Two patients required hospitalization for Grade III radiation pneumonitis. We conclude that the delivery of precisely targeted, high dose, hypofractionated irradiation to lung tumors with the CyberKnife is well tolerated and has outcomes that are comparable with published results for other methods of SBRS.

In this article we review many important epigenetic changes in early carcinogenesis and discuss the possibility of these alterations being targeted for therapeutic intervention in the future. Both regional DNA methylation and global chromatin packaging are interrelated partners that function in concert to control gene transcription. We first summarize briefly DNA methylation and its role in gene expression. Then, we focus on how the DNA is packaged into chromatin and the tight relationship between chromatin and DNA methylation. A more complete understanding of these key, regulatory events is vital in approaching a more rational drug therapy to various malignancies.

A database of Department of Defense diesel engine powered off-road equipment was developed using Micro-soft Access database development tools. The database contains information about fuels, equipment, engines, inventories, usage, and fuel consumption that was obtained from many disparate sources. This database was developed to support the SERDP-funded project Characterization of Off-Road Emissions of Criteria Pollutants (WP-1336). The database was used to prioritize the equipment contained in the WP-1336 test matrix and will later be used as a source of information for the WP-1336 engine emission estimation tool. Data analysis has shown that the top ten fuel consuming engines account for more than 90 percent of fuel usage for the Army and more than 80 percent for the U.S. Marine Corps. Therefore, emission tests performed on a limited number of off-road diesel engines can provide a fairly complete picture of emissions from the entire population of military off-road sources. The database includes an interface that allows users to view data in onscreen forms or analyze data using built-in reports. The database and interface are intended as resources for anyone interested in examining, filtering, querying, or analyzing the collected data.

High-efficiency gas-fired cooling equipment is readily available for commercial, institutional, and industrial facilities. Natural gas engine-driven chillers have higher coefficients of performance of any natural gas cooling system and can serve as energy efficient alternatives for new electric chillers. This study monitored the performance of natural gas cooling technologies operating at Warner-Robins Air Force Base, GA during the fiscal year 2000 cooling season and compared the actual performance data to theoretical values. Energy and demand cost analyses were performed to compare natural gas cooling technology with the energy and demand costs of old and new electric chillers. The study determined that, at the monitored base, the costs for the natural gas used by the engine-driven chillers were lower than electrical costs used by old and new electric chillers, resulting in an energy cost savings.

The Army has programmed $60 million per year from FY98 through FY02 for the Central Heat Plant (CHP) Modernization Program. The purpose of the program is to modernize old and failing heating plant and distribution equipment so that they will provide installations with reliable, safe, energy efficient, environmentally friendly service. This report includes a program status update and documents the site surveys and analyses that were conducted for the program during FY98. This report also includes guidance for installation DPWs on developing and analyzing modernization projects and preparing the DD Form 1391.

Based on its experience with a cogeneration project at Tyndall AFB, the Air Force Civil Engineering Support Agency (AFCESA) tasked the U.S. Army Construction Engineering Research Laboratories (USACERL) to perform an analysis to see if such a concept, or some other cooling options, could be of economic benefit at the Air Force medical facility at Davis-Monthan AFB, AZ, where the cost of purchased electrical power is relatively high compared to that of natural gas. USACERL researchers developed a cooling load profile for the facility by reviewing plant records and interviewing plant operators. Boiler logs (daily and monthly) were consulted to determine heating loads, and a spreadsheet was developed to analyze nine options. Savings and first costs were input into the Life Cycle Cost in Design (LCCID) computer program to determine simple paybacks and savings-to-investment ratios for all options. Based on the results of the investigation, preferred options were recommended for meeting the facility cooling load.

High-efficiency gas-fired cooling equipment is readily available for commercial, institutional, and industrial facilities. Natural gas engine-driven chillers have higher coefficients of performance than any natural gas cooling system and can serve as energy efficient alternatives for new electric chillers. This study monitored the performance of natural gas cooling technologies operating at three Air Force bases during the fiscal year 1998 cooling season and compared the actual performance data to theoretical values. Energy and demand cost analyses were performed to compare each natural gas cooling technology with the energy and demand costs of old and new electric chillers. The study determined that, at the monitored bases, the costs for the natural gas used by the engine-driven chillers were lower than electrical costs used by old and new electric chillers, resulting in an energy cost savings.

In the United States, juvenile neuronal ceroid-lipofuscinosis (JNCL) is the most common form of NCL. This study analyzed 191 cases, diagnosed on the basis of age-at-onset, clinical symptomatology, and pathologic findings. Twenty percent (40/191) of these cases from 24/120 families manifested atypical clinical symptomatology and/or pathologic findings (typical revealed fingerprints and atypical revealed mixed inclusions, or only curvilinear or granular profiles) and, therefore, represent variant forms of JNCL. Those patients in the study with typical JNCL were a uniform group of cases, whereas the atypical were heterogenous and were divided into 8 subgroups based on the clinicopathologic findings. Forty-three families were analyzed (27 typical, 16 atypical) for the common 1.02 kb deletion and several pedigrees for novel mutations. In typical JNCL the common 1.02 kb deletion in both alleles (homozygous) were observed in 23/27, and only 1 allele (heterozygous) was exhibited in 4/27 families. In atypical JNCL families, 5/16 were heterozygous for the common 1.02 kb deletion. None of the remaining 11/16 families had the common 1.02 kb deletion in either allele, but in 9/11 cases the palmitoyl-protein thioesterase (PPT) levels were deficient. In cases where the mutation in CLN3 gene has not been identified, several possibilities may exist. The phenotype may be caused by a yet undefined mutation in CLN3 or may be due to overlapping with other forms of NCL.

Approximately one-third of all energy consumption and two-thirds of total energy expenditures at Department of Defense fixed facilities are electricity related. Electrical energy costs can be reduced by conserving electrical energy or by replacing electrical consuming devices with alternate fuel-driven mechanisms, e.g., by natural gas cooling. Use of state-of-the-art gas cooling technologies can reduce an installation's electric demand, provide domestic hot water, and lessen environmental impacts normally attributed to electric-driven chillers. This study evaluated absorption chillers, engine-driven chillers, and desiccant dehumidification systems as possible alternatives to electric cooling equipment at Air Force facilities. Site candidates were screened, economic costs/benefits analyses of applying gas cooling technologies at specific locations were done, and new equipment was purchased, installed, and tested at approved sites. Recommendations were made regarding the use of gas cooling technologies at Air Force facilities as a whole.

We investigate the electric field produced in a ferroelectric ceramic disk polarized in the axial direction when it is subjected to uniform transient loading over one of its planar surfaces. It is shown that the structure of the electric field depends on the instantaneous piezoelectric response, the degradation of the piezoelectric response due to the time dependent effects of depoling, and the structure of the mechanical disturbance. For the situation when electric field‐strain relaxation is much faster than stress‐strain relaxation, the voltage obtained by integrating the calculated electric field is in excellent qualitative agreement with the observed behavior of PZT 65/35.

SUMMARY 1. One hundred and forty-six infants with congenital esophageal atresia, tracheoesophageal fistula, or both, were observed on the endoscopic service of The Children's Memorial Hospital between 1947 and 1964. One hundred and twenty-three, or 84.2 per cent, were Type III, 12 were Type IV (“H”), and 10 were Type I with both segments blind. One had an esophageal atresia with both upper and lower segments entering the trachea. 2. Laryngeal problems included congenital anomalies, paralyses, and postoperative edema. Twelve infants had laryngeal paralyses: 6 bilateral, 2 right and 4 left cord paralysis. Laryngeal paralysis invariably increased the respiratory and deglutition difficulties of the postoperative period. 3. Tracheal problems included congenital tracheomalacia and stenoses. The most serious post-surgical complications occur at the site of the fistula leading to the lower esophageal segment. Obstruction due to inversion of the edges, granulomas, and too tight a closure were present in 14 infants. Diverticula, consisting of a residual piece of the lower esophageal segment not completely removed, were found in 11 infants. There were 12 recurrent tracheoesophageal fistulas. 4. Bronchial secretions, chemical bronchitis, and atelectasis constitute the principal bronchopulmonary complications. These appear to increase in severity with delay in closure of the tracheoesophageal fistula. The alteration of respiratory physiology associated with resection of portions of several ribs may play a part in increasing the severity of the bronchopulmonary problems. 5. Esophageal strictures were present in 103 of the 146 infants; 93 at the site of a direct end-to-end anastomosis, 8 at the esophagogastric, -colic, or -jejunal site, and 2 at the cologastric site. Early recognition and treatment of the narrowing lumen in the immediate postoperative period is stressed. Swallowing function is usually normal until semisolids are added to the infant diet, at which time the anastomosis stricture is already firm and tough. Techniques of bougienage in the early postoperative period and management of the late fibrous strictures are outlined. 6. Reanastomosis was necessary in 6 infants because of inability to reestablish a lumen endoscopically. All were dilated early in the postoperative period following the revision and have attained a normal swallowing function.

The sine que non for a successful repair of large omphaloceles, gastroschisis, and large ventral hernias is the gradual replacement of the viscera into the contracted abdominal cavity. A satisfactory method is a staged surgical approach using dacron reinforced Silastic sheets. The experimental and clinical uses of these sheets are described.

We describe a series of experiments to examine emissions in the radio-frequency (RF) portion of the electromagnetic spectrum, resulting from hyper-velocity impacts of various metals. A two-stage gas gun was used to impact aluminium (6061-T6) spheres, at velocities of approximately 6 km/s and 9 km/s, against aluminium/titanium alloy (Ti6Al4 v) target plates. In most experiments, debris ejected from the rear surfaces of target plates impacted against witness plates of various metals (aluminium, copper, zinc, etc). The witness plates were placed at various distances from rear surfaces of target plates, and electric field probes were used to obtain measurements of three near-field orthogonal components of the electric fields at sampling rates of 10 giga-samples/s. From experimental and computational results, we have developed a semi-empirical model describing dependence of the electric field amplitude and frequency on material strength and impact conditions.

The consumption of lithium salts has increased appreciably over the past few years, reflecting an almost universal acceptance of the pre-eminent efficacy and specificity of the lithium ion in extinguishing and controlling primary affective disturbances without altering adversely cognitive or affective functioning. An appreciably large number of psychiatrists not only treat manic and depressive patients with lithium where indicated, but also serve as consultants to an increasing number of general practitioners who now provide direct clinical care for patients on prophylactic or maintenance lithium. Unsurprisingly, the increase in the clinical use of lithium over the past 10 years is paralleled by a concomitant increase in the number and variety of reported side-effects, both innocuous and transient, as well as by reports of the more serious lithium intoxication.

A numerical procedure has been developed to obtain information regardig the hypervelocity impact of a sphere onto a plate by considering the corresponding plane strain problem The method consists of treating a rod as a superposition of an infinite chain of spheres and then numerically unfolding information about a single sphere. This technique has been used to calculate the peak pressure distribution when the impact is normal to the plate surface and excellent results were obtained. When extended to oblique impact problems, physically reasonable results are obtained but at this time no independent checks are available.

Four children with fusiform venous aneurysms in the neck are described. Two had aneurysms of the internal jugular vein and two had aneurysms of the superficial communicating veins. The diagnosis can be suspected when a venous hum is heard over a neck mass that expands with the Valsalva maneuver. The preoperative diagnosis is confirmed by arteriography or venography. Three of the aneurysms were removed for cosmetic reasons and one is being followed.

This paper discusses the new relationship between Government and the Scientific Estate, and the three urgent tasks facing the Scientific Community, including the role of the Scientist in meeting the awesome and challenging social problems of our time. Many of these problems are directly attributable to the development and abuse of modern technology.

CIRCULATORY FAILURE may be further aggravated by the use of vasopressor amines in the management of shock.1Reversible shock may be converted to an irreversible state, and treatment directed at blood pressure elevation utilizing these agents may result in multiple foci of necrosis in visceral organs in the absence of demonstrable vascular occlusion.2,3The histories presented are of two patients in whom, after prolonged shock, ischemic necrosis of the liver, intestines, and spleen was found at autopsy. A concept of the development of these lesions is presented. Report of Cases Case 1.— A 46-yr-old female with established rheumatic mitral valvular disease entered Chicago Wesley Memorial Hospital for a mitral valvuloplasty. Interpretation of a cardiac catheterization done 1 week prior to surgery indicated that she was suffering from severe mitral stenosis with mild insufficiency. Right-heart-catheterization data suggested tricuspid insufficiency and right-heart failure. A mitral commissurotomy was performed and

To the Editor:— We thank Dr. Nigogosyan for his interest in our cases. At the time we submitted our paper toThe Journal, the correlation between halothane (Fluothane) anesthesia and liver necrosis had just come to our attention, and we therefore considered the possibility of a relationship in our cases. In case 1, the anesthetic was cyclopropane. In case 2, halothane was used in both surgical procedures, but at no time during either was hypotension or any other abnormality noted. Not until 9 days after the second operation (for perforated peptic ulcer) did hypotension, hematemasis, and bloody diarrhea develop in the patient. If the anesthetic agent was responsible for the liver necrosis found at autopsy, one would have expected a more rapid onset of symptoms after the administration of the gas, rather than a prolonged course of 9 days as our patient experienced. In addition, the well-known hepatotoxic agents such