Donor-derived Trypanosoma cruzi infection in solid organ recipients in the United States, 2001-2011.

Although Trypanosoma cruzi, the parasite that causes Chagas disease, can be transmitted via organ transplantation, liver and kidney transplantation from infected donors may be feasible. We describe the outcomes of 32 transplant recipients who received organs from 14 T. cruzi seropositive donors in the United States from 2001 to 2011. Transmission was confirmed in 9 recipients from 6 donors, including 3 of 4 (75%) heart transplant recipients, 2 of 10 (20%) liver recipients and 2 of 15 (13%) kidney recipients. Recommended monitoring posttransplant consisted of regular testing by PCR, hemoculture, and serology. Thirteen recipients had no or incomplete monitoring; transmission was confirmed in five of these recipients. Four of the five recipients had symptomatic disease and all four died although death was directly related to Chagas disease in only one. Nineteen recipients had partial or complete monitoring for T. cruzi infection with weekly testing by PCR, hemoculture and serology; transmission was confirmed in 4 of 19 recipients with no cases of symptomatic disease. Our results suggest that liver and kidney transplantation from T. cruzi seropositive donors may be feasible when the recommended monitoring schedule for T. cruzi infection is followed and prompt therapy with benznidazole can be administered.

Pallister-Killian and Fryns syndromes: nosology.

Fryns syndrome is a lethal autosomal recessive multiple congenital anomaly syndrome characteristic "coarse" facies, cleft palate, diaphragmatic hernia, and distal digital hypoplasia. The appearance of the face and digits is very similar to that observed in Pallister-Killian syndrome (mosaic isochromosome 12p), although the incidence of cleft palate, diaphragmatic hernia, and neonatal death is much lower in the latter condition. We report on an infant with many manifestations of Fryns syndrome ("coarse" face, cleft palate, cloudy corneae, diaphragmatic hernia, distal digital hypoplasia, and neonatal death) who was found to be mosaic for i(12p). Her diagnosis was changed to Pallister-Killian syndrome and the family was counselled accordingly. The clinical overlap between Fryns and Pallister-Killian syndromes is discussed. Because the chromosome abnormality in Pallister-Killian syndrome is often limited to fibroblasts and may be selectively eliminated both in vivo and in vitro, some Pallister-Killian patients may be misdiagnosed with Fryns syndrome and given an erroneously high recurrence risk. Newborn infants with the Fryns or Pallister-Killian phenotypes should have chromosome studies involving multiple tissues so that the correct diagnosis can be made. This will contribute to the understanding of both disorders and facilitate appropriate genetic counselling.

Surgical approaches of the rearfoot and ankle.

The number of alternative approaches for the variety of rearfoot and ankle procedures commonly performed is clearly as great as the imagination of the surgeon. To ensure that the incisional approach is to contribute to the overall success of the procedure, the right approach must be selected and properly performed. To facilitate this process, general principles of incision placement and performance in the rearfoot and ankle have been presented. Building on those principles, one can learn the various techniques, as well as their respective advantages and disadvantages. Finally, the discerning surgeon should be able to apply the information presented here to select and perform the right incisional approach. Furthermore, the same process may lead the surgeon to improvise and create a successful alternative.

Model for the genetic evolution of human solid tumors.

A conceptual model is proposed for the genetic evolution of many human solid tumors that is based on the observations that cancer cells may spontaneously double their chromosome number; that cells with excessive chromosome numbers may be cytogenetically unstable, both losing chromosomes randomly during subsequent cell divisions, and often developing structural abnormalities in the chromosomes that are retained; and that some structural chromosome abnormalities may activate growth-promoting genes. The sequence of tetraploidization with chromosome loss can occur repeatedly in a given tumor. The available evidence supporting the model is reviewed. A computer simulation system that embodies these concepts is described and the model is used to generate distributions of chromosome number/cell under various simulated conditions and in a variety of simulated biological settings. A simulation of the time course of changes in chromosome number per cell that accompany the spontaneous neoplastic transformation of mouse fibroblasts in vitro is described. The best fit to the data was obtained when provision was made for the activation of at least two growth-promoting genes. The conditions for generating discrete aneuploid peaks in cytogenetic and flow cytometric studies were explored; our modeling studies suggest that the activation of a growth promoting gene is required in order to produce a discrete aneuploid peak. Our modeling studies suggest that the overrepresentation of individual oncogene-bearing chromosomes in aneuploid cell lines may require the activation of gene dose-dependent growth-promoting genes and is not likely to occur in cell lines in which at least two copies of each normal chromosome are required for cell survival. Overall, the results obtained using the model are consistent with a wide variety of flow cytometric and cytogenetic studies in human solid tumors.

Karyotypic evolution of a human undifferentiated large cell carcinoma of the lung in tissue culture.

Serial cytogenetic studies were performed on a cell line derived from a pleural effusion from a patient with undifferentiated large cell carcinoma of the lung. The initial sample had a broad range of chromosome numbers per cell, with a hypodiploid/pseudodiploid stem line and a hypotetraploid sideline. A sequence consisting of a doubling of chromosome number per cell followed by chromosome loss was observed repeatedly during 40 culture passages. The presence of metaphase spreads showing evidence of endoreduplication suggested this as a likely mechanism for the doubling of chromosome number per cell. Eleven marker chromosomes were observed in the cells of the primary sample; these markers persisted through all subsequent passages. Chromosomes 1, 2, 6, 7, 8, 11, and 16 were consistently overrepresented; each of these chromosomes was involved in marker formation. Chromosomes 4, 5, 9, 10, 19, 21, and 22 were consistently underrepresented. Every chromosome, either in its normal form and/or as part of a marker, was represented on the average by at least one copy per diploid cell. Eighteen new marker chromosomes were observed during the course of cell cultivation; one of these evolved into a clonal marker over the course of six cell passages. Of the new marker chromosomes that were formed during the observation period, the majority were found in hypotetraploid cells.

Ultrasonic assessment of skin and wounds with the scanning laser acoustic microscope.

The aim of the present study was to test the hypothesis that ultrasonic propagation properties in skin and wound tissue would correlate with material properties such as collagen content, water content, and tensile strength of those tissues. Both ultrasonic speed and ultrasonic attenuation coefficient were directly correlated with tissue collagen content, [r = 0.80 and r = 0.56, respectively (p less than 0.001)]. In addition, ultrasonic speed and attenuation coefficient were inversely correlated with tissue water content, [r = -0.57 and r = -0.73, respectively (p less than 0.001)]. Tensile strength also correlated very significantly with ultrasonic speed (r = 0.90, p less than 0.001), and significantly with attenuation coefficient (r = 0.58, p less than 0.001). The results demonstrate the feasibility of using ultrasound for noninvasively determining the material properties of biologic tissues including healing cutaneous wounds.

Increased chromosomal aberrations in first metaphases of cells isolated from the kidneys of aged mice.

Chromosomal aberrations were scored in the first metaphases of cells isolated from the kidneys of young (8 months old) and aged (40 months old) CB6F1 mice. There was a sixfold increase in the frequency of such aberrations in metaphases from old mice as compared with young mice.

Restrainer and cell for dermal dosing of small laboratory animals.

A versatile small animal restrainer and glass dermal dosing cell were designed for use in metabolism studies of dermally applied chemicals. Through use of the restrainer it was possible to apply a chemical to the skin of an unanesthetized rat and leave it there for hours or days without contact between the application site and the restrainer. The dermal dosing cell, when affixed to the skin of a restrained rat, formed a non-occlusive covering for the dermally applied dose and prevented contamination of excretion products by flaking of the applied dose or by desquamation of dosing site skin.