Successive Implants Research Articles

Determination of patient-specific airway stent fit using novel 3D reconstruction measurement techniques: a 4-year follow-up of a patient.

Managing complex benign airway disease is a major challenge in interventional pulmonology. With the introduction of additive manufacturing in the medical field, patient-specific (PS) implants are an innovate prospect for airway management. Historically, stents were oversized to resist migration. However, the optimal degree and impact of stent oversizing remains unclear. The ability to design stents based on computed tomography (CT) invites opportunity to understand sizing. Here, we report a novel three-dimensional (3D) image reconstruction tool to quantify fit repeatedly over time. Analysis of CT imaging before and after successive stent implants in a single patient with different areas of stenosis and malacia was done. Nine PS airway stents over 4 years (five left mainstem and four right mainstem) were studied. The distance between the airway model and stent was calculated. The CT images were correlated to stent designs in CloudCompare software (v2.10-alpha) for novel analysis. Heat map was exported depicting the distances between the airway and the stent to the clinician's prescribed stent model. Corresponding histograms containing distances, mean, and standard deviation were reported. It is possible to measure stent fit based on heat map quantification on patient imaging. Observation of the airway over time and stent change suggests that the airway became more open over time requiring increased stent diameters. The ability to design and measure stent fit over time can help quantify the utility and impact of PS silicone airway stent. The airway appears to display plasticity such that there is notable change in stent prescription over time.

Predictors of 1-year survival in South African transcatheter aortic valve implant candidates.

Transcatheter aortic valve implantation (TAVI) has undergone rapid expansion internationally over the past 15 years. In view of resource constraints in developing countries, a major challenge in applying this technology lies in identifying patients most likely to benefit. The development of a risk prediction model for TAVI has proved elusive, with a reported area under the curve (AUC) of 0.6 - 0.65. The available models were developed in a First-World setting and may not be applicable to South Africa (SA). To evaluate novel indicators and to develop a TAVI risk prediction model unique to the SA context. The current work represents the important initial steps of derivation cohort risk model development and internal validation. Seven-year experience with 244 successive TAVI implants in three centres in Western Cape Province, SA, was used to derive risk parameters. All outcomes are reported in accordance with the Valve Academic Research Consortium definitions. Multiple preprocedural variables were assessed for their impact on 1-year survival using univariate and multivariate models. Factors found not to correlate with 1-year survival included age, renal function and aortic valve gradients. The commonly used surgical risk prediction models (Society of Thoracic Surgeons score and EuroSCORE) showed no correlation with outcomes. Factors found to correlate best with 1-year survival on multivariate analysis were preprocedural body mass index (BMI) (favouring higher BMI), preprocedural left ventricular end-diastolic dimension (LVED) and ejection fraction (EF) (favouring smaller LVED and higher EF), absence of atrial fibrillation, and three novel parameters: independent living, ability to drive a car, and independent food acquisition/cooking. Discriminant analysis of these factors yielded an AUC of 0.8 (95% confidence interval 0.7 - 0.9) to predict 1-year survival, with resubstitution sensitivities and specificities of 72% and 71%, respectively. Apart from existing predictors, we identified three novel risk predictors (independent living, ability to drive a car, and independent food acquisition/cooking) for 1-year survival in TAVI candidates. These novel parameters performed well in this early evaluation, with an AUC for predicting 1-year survival higher than the AUCs for many of the internationally derived parameters. The parameters are inexpensive and easy to obtain at the initial patient visit. If validated prospectively in external cohorts, they may be applicable to other resource-constrained environments.

The use of contraceptive techniques in managed wild African lion (Panthera leo) populations to mimic open system cub recruitment

Context Managed wild lions (Panthera leo) are lions found in smaller (<1000 km2), fenced protected areas that hold a substantial portion of South Africa’s wild lion population. Because the natural population control mechanisms are compromised within these properties, managers must actively control population growth rates. Fecundity control is used by wildlife managers, but long-term, empirical data on the impact and consequences of such interventions in lions are lacking. Aims The aim of the present study was to assess the effectiveness of two methods of contraception (deslorelin implant and unilateral hysterectomy) in reducing cub recruitment of managed wild lions. Methods Survey data spanning 14 years from 94 managed wild lions on 19 protected areas were used to evaluate the effectiveness of deslorelin implant treatments and unilateral hysterectomies on population growth rates through mimicking open system cub recruitment. Key results Deslorelin implants were effective at increasing the age of first reproduction and lengthening inter-birth intervals. There was also an unexpected decrease in litter size. Behavioural side-effects were recorded in 40% of individuals: 19% pride fragmentation; 13% lack of receptiveness towards males; 8% other. The more successive deslorelin implants a lioness had, the more likely it was that weight gain was reported. Unilateral hysterectomy resulted in a decrease in litter size post-surgery, but this was not statistically significant. No behavioural or physiological side-effects were noted after unilateral hysterectomy. Conclusions Deslorelin treatment was more effective in reducing the reproductive output of managed wild lionesses than unilateral hysterectomy surgery. While more side-effects were associated with deslorelin implants than unilateral hysterectomies, a single deslorelin treatment is currently a good option for fecundity reduction. More research is required on unilateral hysterectomy surgery. Implications Neither deslorelin implants nor unilateral hysterectomies offer a ‘silver bullet’ solution for reducing rapid population growth in managed wild lions. Reproductive control should be integrated with other best-practice approaches.

Microencapsulation of Parathyroid Cells for the Treatment of Hypoparathyroidism.

Cell encapsulation is an alternative to avoid rejection of grafted tissue, thus bringing an interesting alternative in cell therapy. It is particularly relevant in ailments where only the implant of small quantities of tissues is warranted. In such circumstances, the use of immunosuppressive therapy in patients implanted with tissues from donors is debatable, yet unavoidable at present in order to prevent rejection and/or sensitization of the host to the tissue, in turn jeopardizing the success of successive implants. Hence, a new line of thought, which aims to provide an immunoprivileged site for the grafted tissue, while at the same time insure its nutrition, as well as its survival and continued function, appears as a most attractive possibility. To achieve these goals, cells or tissues harvested for transplant could be encapsulated in biologically compatible matrices. Among the matrices currently in existence, sodium alginate is the most widely used polymer for tissue encapsulation.In the present chapter, we present a technique used to encapsulate parathyroid tissue, for use as cell transplant therapy in patients with secondary hypoparathyroidism. With this procedure, implanted tissue survives and remains functional for up to 18 months.

Abstract B06: Knock-down of H3.3 K27M mutant protein in DIPG cells delays, but does not abrogate, tumor growth in vivo

Abstract Genome-wide sequencing efforts of pediatric high grade gliomas (HGG) identified recurrent and hotspot mutations in the N-terminal regulatory tail of histone H3 variants H3.3 (H3F3A) and H3.1 (HIST1H3B/C). K27M histone mutations are mainly observed in midline tumors, including 78% of diffuse intrinsic pontine gliomas (DIPGs). By contrast, G34R/V mutations are predominantly restricted to 15% of the hemispheric tumours. This illustrates a highly specific selective pressure for each mutation in different cell types during brain development. The K27M mutation induces a dominant negative loss of trimethylated K27 (H3K27me3) marks in the bulk H3 pool. H3K27me3 interacts with Polycomb repressive complex 2 (PRC2) to repress transcription of target genes, a key process in the regulation and development of stem cells. Global gene expression analysis revealed that many significant differences between DIPGs (mostly K27M mutants) and non-brainstem pediatric HGG (mostly wild-type) are in genes that encode transcription factors and genes associated with developmental processes. Importantly, there was particular enrichment of genes exclusively expressed in distinct developing brain locations. Hence, it is challenging to define a clear gene expression signature associated with K27M mutations in DIPGs. In this study, in order to identify factors directly regulated by K27M, we aimed to knock-down the mutated protein in a DIPG-derived xenograft line. This H3.3 K27M line is maintained by successive implants of luciferase+/YFP+ tumor cells in the cortex of CD-1 nude immunocompromised mice. Resected tumor cells were transduced with lentiviral vectors expressing H3F3A specific shRNAs, selected with puromycin in neural stem cell culture conditions, and either kept under culture or re-implanted into mice. Cells in culture expressing any of three distinct shRNAs showed 92-96% H3F3A mRNA knock-down, 82-90% K27M protein knock-down and a 4-7 fold increase in H3K27me3 levels. Knock-down of H3F3A with any of three shRNAs in vivo significantly extended the time for tumor growth and the survival of xenografted mice. Notably, tumor growth was not completely abrogated. We observed an average of 79% H3F3A mRNA knock-down and increased levels of H3K27me3 by immunofluorescence in experimental tumors. Global gene expression profiling revealed modulation of a common subset of genes by all three shRNAs in vivo. We will present analysis of the gene expression changes associated with loss of the K27M mutation in DIPG cells. Overall, we show efficient knock-down of H3F3A in a H3.3 K27M mutant DIPG-derived xenograft line, leading to increased accumulation of H3K27me3, modulation of gene expression, and increased survival in vivo. Citation Format: André B. Silveira, Xiaoyan Zhu, Chunxu Qu, Suzanne Baker. Knock-down of H3.3 K27M mutant protein in DIPG cells delays, but does not abrogate, tumor growth in vivo. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B06.

Associations of genetic markers in cattle receiving differing implant protocols1,2

The potential interaction of growth-promoting implants and genetic markers previously reported to be associated with growth, carcass traits, and tenderness was evaluated. Two implant protocols were applied to subsets of steers (n = 383) and heifers (n = 65) that were also genotyped for 47 SNP reported to be associated with variation in growth, fat thickness, LM area, marbling, or tenderness. The "mild" protocol consisted of a single terminal implant [16 mg estradiol benzoate (EB), 80 mg trenbalone acetate (TBA) or 8 mg EB, 80 mg TBA given to steers and heifers, respectively]. The "aggressive" protocol consisted of both a growing implant (8 mg EB, 40 mg TBA) for the lightest half of the animals on the aggressive protocol and 2 successive implants (28 mg EB, 200 mg TBA) given to all animals assigned to the aggressive treatment. Implant protocol had measurable impact on BW and ADG (P < 0.05), with the aggressive protocol increasing these traits before the terminal implant (relative to the mild protocol), whereas the mild protocol increased ADG after the terminal implant so that the final BW and ADG over the experimental period were similar between protocols. Animals on the aggressive protocol had significantly increased (P < 0.05) LM area (1.9 cm(2)), slice shear force (1.4 kg), and intact desmin (0.05 units), but decreased (P < 0.05) marbling score (49 units) and adjusted fat thickness (0.1 cm), and yield grade (0.15 units). Among both treatments, 8 of 9 growth-related SNP were associated with BW or ADG, and 6 of 17 tenderness-related SNP were associated with slice shear force or intact desmin. Favorable growth alleles generally were associated with increased carcass yield traits but decreased tenderness. Similarly, favorable tenderness genotypes for some markers were associated with decreased BW and ADG. Some interactions of implant protocol and genotype were noted, with some growth SNP alleles increasing the effect of the aggressive protocol. In contrast, putative beneficial effects of favorable tenderness SNP alleles were mitigated by the effects of aggressive implant. These type of antagonisms of management variables and genotypes must be accounted for in marker assisted selection (MAS) programs, and our results suggest that MAS could be used to manage, but likely will not eliminate negative impact of implants on quality.

Effect of repeated administration of combination trenbolone acetate and estradiol implants on growth, carcass traits, and beef quality of long-fed Holstein steers.

Our objective was to determine the effect of repeated use of implants on feedlot performance and carcass characteristics of Holstein cattle. Holstein steers (n = 128) weighing an average of 211 kg were blocked by weight and randomly assigned to 16 pens. At the start of the trial (d 0), pens were assigned to one of four treatments: 1) nonimplanted control (C); 2) implant on d 0, 112, and 224 (T3); 3) implant on d 112 and 224 (T2); and 4) implant on d 224 (T1). Component TE-S implants (120 mg of trenbolone acetate and 24 mg of estradiol per implant) were used for all treatments during the 291-d feeding period. Over the course of the study, T2 and T3 cattle had greater ADG and final weights than C and T1 cattle (P < 0.05). Steers were harvested at a commercial abattoir on d 291. Hot carcass weights of T3 steers were greater than those of C and T1 steers (P < 0.05). Dressing percentage, adjusted 12th-rib fat, percentage of kidney, pelvic, and heart fat, yield grade, and longissimus color were not different among treatments (P > or = 0.26). Longissimus muscle areas (LMA) of T2 and T3 carcasses were larger than LMA of C (P < 0.01). No USDA Select carcasses were produced from C cattle, whereas the percentage of Select carcasses from implanted cattle ranged from 10 to 18%. Skeletal maturity advanced (P < 0.05) progressively with each additional implant. Steaks from T3 carcasses had a higher percentage of protein than controls (P < 0.05) and were less tender than all other treatments (P < 0.05). Repeated administration of combination trenbolone acetate and estradiol implants increased ADG and resulted in heavier carcasses with larger LMA. Administration of three successive implants decreased tenderness of Holstein beef, and resulted in more advanced skeletal maturity scores.

Prostate-seminal vesicle cancers induced in noble rats.

Susceptibility of Noble strain rats to induced cancers in the accessory sex glands was determined. Following an IV inoculation of methylnitrosourea plus three successive SC implants of testosterone propionate, early stage adenocarcinomas were observed in the seminal vesicles and anterior prostates, but not in the dorsolateral nor in the ventral lobes.

Structural and photoluminescence studies of Er implanted Be doped and undoped low-temperature grown GaAs

Characteristic 1.54 μm Er3+ emission has been observed from Er-implanted and annealed, low-temperature grown GaAs Be doped and undoped samples. Er plateau implantations (480, 155, and 40 keV successive implants) were performed at 300 °C covering calculated Er concentrations from 1018 up to 1020 Er/cm3. Cross-sectional transmission electron microscopy studies reveal very little structural damage for these elevated temperature implants up to an Er total fluence of 1.36×1014 Er/cm2. No Er emission was observed from any of the as-implanted samples but it was observed after postimplantation annealings at 650 and 750 °C temperatures. The Er emission was significantly more intense after 650 °C anneals, for Be doped samples, and after 750 °C anneals for undoped samples. It appears on top of a broad background luminescence associated with midgap states. The Er emission intensity was found to scale linearly with the total Er implantation fluence up to Er concentration of ∼1019 Er/cm3. Er precipitation was observed after 750 °C annealing for 1019 Er/cm3 samples, but could be observed for 1020 Er/cm3 Er-doped samples even after a 650 °C anneal. These precipitates are most likely ErAs.

Implant program effects on performance and carcass quality of steer calves finished for 212 days.

We compared the effects of seven implant treatments combining use of Ralgro (RAL), Synovex-S (SYN), and Revalor-S (REV) on performance and beef quality traits of crossbred steer calves (n = 560) finished for 212 d. A randomized complete block design was used to compare treatments consisting of 1) non-implanted control (CON); 2) RAL on d 0, SYN on d 60, and REV on d 130 (RALSYNREV); 3) RAL on d 0, REV on d 60, and REV on d 130 (RALREVREV); 4) SYN on d 30 and REV on d 130 (SYNREV); 5) REV on d 30 and REV on d 130 (REVREV); 6) REV on d 0, REV on d 75, and REV on d 150, 12.5% crude protein diet (REV3X-12.5); and 7) REV on d 0, REV on d 75, and REV on d 150, 14.5% crude protein diet (REV3X-14.5). All implant groups had higher ADG and gained more efficiently (ADG: feed intake) than the CON group. No distinct performance advantages were noted for particular implant schemes. Implant treatments did not (P > .05) affect dressing percentage, carcass weight, or KPH fat percentage. Fat thickness did not differ (P > .05) for implanted vs CON steers; however, REVREV, SYNREV, and RALREVREV steers produced fatter carcasses than did REV3X-12.5 and RALSYNREV steers. The REV3X-12.5 and REV3X-14.5 treatments increased longissimus muscle area compared with CON; longissimus muscle areas for all other treatments did not differ (P > .05) from CON. No reduction in percentage of Choice and Prime carcasses occurred with use of SYNREV or REVREV; however, all treatments receiving three successive implants had lower (P < .05) percentages of Choice and Prime carcasses than the CON group. Increasing dietary crude protein seemed to lessen the detrimental effect of three successive REV implants on percentages of Choice and Prime carcasses. Loin steaks from REVREV, REV3X-12.5, and REV3X-14.5 steers had higher (P < .05) shear force values than steaks from CON steers.

Enhanced compositional disordering of quantum wells in GaAs/AlGaAs and InGaAs/GaAs using focused Ga+ ion beams

Spatially selective compositional disordering induced by focused Ga+ ion beam implantation in GaAs/AlGaAs and strained InGaAs/GaAs quantum well structures has been studied using photoluminescence. We find that beyond a certain implantation dosage, the degree of intermixing imparted to a given quantum well saturates and may eventually decline as a result of damage to the semiconductor surface. We overcome this limitation by thermally annealing the sample after implantation to repair the crystalline surface. We show that multiple successive implants interspersed with rapid thermal anneals (RTAs) are successful in locally shifting the optical band gap of quantum wells by many times that attributed to a single implant and RTA.

The Total Artificial Heart

In the early 1800s, an awareness of potential ventricular failure stimulated interest in artificial heart replacement. In 1937 the first total artificial heart (TAH) was implanted into the chest of a dog by Russian physicians. The primary driving force for mechanical cardiac assistance developed from the necessity for circulatory assistance in order to perform corrective cardiac surgery. In 1953 the first successful closure of an atrial septal defect using extracorporeal circulation was performed. During the following decade the concept of using mechanical devices to assist the failing heart was aggressively pursued. This culminated in the first implant of a TAH in a human in 1969 as a bridge to transplant. Clinical implant of the TAH as a permanent device was performed in 1982 by researchers at the University of Utah. This patient lived for 112 days. Three successive permanent implants were performed in Louisville, Kentucky, with one patient surviving for 620 days. All of these permanent TAH patients suffered from device-related complications including bleeding, infection, and thromboembolic events. It became apparent that the present configuration of the TAH with its external drive lines and large air console was not ideal for long-term support. In 1985 the first implant of the Symbion J-7-100 TAH (Jarvik-7) as a bridge to transplant was performed. This patient was supported by the device for 9 days and was successfully transplanted and discharged home. Since 1985 more than 170 patients have been bridged using the Symbion J-7 TAH with more than 70% of these patients being successfully transplanted. The incidence of thromboembolic events has dramatically reduced with better understanding of anticoagulation requirements. Infection continues to be the greatest potential complication with these patients. In spite of this, the pneumatic TAH has proved to be an adequate bridge to transplant device.

Mentor GFS inflatable prosthesis

A new inflatable penile prosthesis is described. The operative approaches, infrapubic and scrotal, are discussed and compared. The results of 56 successive implants are presented. the simplicity of the device which combines the usual intra-abdominal reservoir and the scrotal pump into a scrotal “resipump” is discussed. The device has shown a good performance and is a valuable addition to the varieties of penile implants.

Myopic astigmatism for increased depth of focus in pseudophakia (author's transl)

The optimal refraction after lens implantation is a slight simple myopic astigmatism for patients wishing to see without glasses. The depth of focus is increased in myopic astigmatism because the shape, rather than the size, of the blurred retinal image changes as Sturm's conoid moves over the retina. Such a refraction can be obtained in pseudophakia if the corneal power change induced by surgery is taken into consideration when the intraocular lens. The induced corneal ametropia is a spherocylinder with a very low equivalent power. The results in a series of 50 successive implants employing these principles are described. The depth of fucus is best in simple myopic astigmatism.

Induction of Male Copulatory behavior in the Brown Leghorn Hen.

SummaryThree cases are described from 4 experimental groups totaling 24 birds, some observed for more than 4 years, in which single comb brown Leghorn hens displayed male copulatory behavior following successive implants of testosterone propionate pellets. Implantations were begun when birds were 4 days, and 1, 3, and 5 months old. These results contrast with earlier negative findings following single daily injections of this hormone. Induction of copulatory behavior in such a small percentage of cases indicates the desirability for further study of factors controlling this behavior pattern.

On the Absorption Rate of Desoxycorticosterone Acetate Pellets

THE USE of pellets of desoxycorticosterone acetate as a means of administering hormone to patients with Addison's disease was first described by Thorn and coworkers in 1939 (1). Since that time numerous reports confirming the efficacy of this mode of treatment have appeared (2–7). Very few of these, however, include data on the actual rate of absorption of the hormone or on variations in the rate of absorption which might be expected in different patients or in the same patient with successive implants. The following report summarizes such data on 11 patients. In 9, Addison's disease seemed a certain diagnosis and was established in every case by physical examination and confirmatory roentgen-ray and laboratory studies. The data on 3 patients have not been included in the charts because in one there was some fragmentation of the pellets and in 2 others the diagnosis was questionable. METHODS Two types of pellets were used.