Implementation of a piritramide based patient-controlled analgesia (PCA) as a standard of care for pain control in late abortion induction: A prospective cohort study from a patient perspective.

Objective: To assess whether the implementation of patient-controlled analgesia (PCA) with piritramide using an automatic pump system under routine conditions is effective to reduce pain in late abortion inductions. Study design: Prospective observational cohort study. Setting: Patients requiring medically indicated abortion induction from 14 weeks of pregnancy onwards between July 2019 and July 2020 at the department of Obstetrics and Prenatal Medicine of the Bonn University Hospital in Germany. Methods: Evaluation of pain management after implementation of a PCA system compared with previous nurse-controlled tramadol-based standard under routine conditions. Patients answered a validated pain questionnaire and requirement of rescue analgesics was assessed. Pain intensity and satisfaction were measured on a ten-point numeric rating scale. Main Outcome Measure Maximal pain intensity. Results: Forty patients were included. Patients using Piritramide-PCA complained of higher pain sores than those in the standard group (6.90 (± 2.34) vs. 4.83 (± 2.87), (p < 0.05)). In both groups the level of satisfaction with the analgesia received was comparable (8.00 (± 2.45) vs 7.67 (± 2.62), (p = 0.7)). Patients in the PCA group suffered more nausea (63.2 % vs 30 % respectively, OR 4.0, 95 % CI 1.05-15.20, p < 0.05) and expressed more the desire for more analgesic support compared to the control group (OR 5.7 (1-33.25), p = 0.05). Conclusion: Women with abortion induction after 14 weeks of gestation suffer from relevant severe pain, which requires adequate therapy. However, addition of PCA does not seem to bring any advantage in patients undergoing this procedure.

A diagnostic support system based on pain drawings: binary and k-disease classification of EDS, GBS, FSHD, PROMM, and a control group with Pain2D.

BACKGROUND AND OBJECTIVE: The diagnosis of rare diseases (RDs) is often challenging due to their rarity, variability and the high number of individual RDs, resulting in a delay in diagnosis with adverse effects for patients and healthcare systems. The development of computer assisted diagnostic decision support systems could help to improve these problems by supporting differential diagnosis and by prompting physicians to initiate the right diagnostic tests. Towards this end, we developed, trained and tested a machine learning model implemented as part of the software called Pain2D to classify four rare diseases (EDS, GBS, FSHD and PROMM), as well as a control group of unspecific chronic pain, from pen-and-paper pain drawings filled in by patients. METHODS: Pain drawings (PDs) were collected from patients suffering from one of the four RDs, or from unspecific chronic pain. The latter PDs were used as an outgroup in order to test how Pain2D handles more common pain causes. A total of 262 (59 EDS, 29 GBS, 35 FSHD, 89 PROMM, 50 unspecific chronic pain) PDs were collected and used to generate disease specific pain profiles. PDs were then classified by Pain2D in a leave-one-out-cross-validation approach. RESULTS: Pain2D was able to classify the four rare diseases with an accuracy of 61-77% with its binary classifier. EDS, GBS and FSHD were classified correctly by the Pain2D k-disease classifier with sensitivities between 63 and 86% and specificities between 81 and 89%. For PROMM, the k-disease classifier achieved a sensitivity of 51% and specificity of 90%. CONCLUSIONS: Pain2D is a scalable, open-source tool that could potentially be trained for all diseases presenting with pain.

Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.

Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.

Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation.

Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αß sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.

Alzheimer's disease drug discovery: in vivo screening using Caenorhabditis elegans as a model for ß-amyloid peptide-induced toxicity.

Alzheimer's disease (AD) is a complex human neurodegenerative disease. Currently the therapeutics for AD only treats the symptoms. While numbers of excellent studies have used mammalian models to discover new compounds, the time and effort involved with screening large numbers of candidates is prohibitive. Cultured mammalian neurons are often used to perform high-throughput screens (HTS); however, cell culture lacks the organismal complexity involved in AD. To address these issues several researchers are turning to the roundworm, Caenorhabditis elegans. C. elegans has numerous models of both Tau and Ab induced toxicity, the two prime components observed to correlate with AD pathology. These models have led to the discovery of numerous AD modulating candidates. Further, the ease of performing RNA interference for any gene in the C. elegans genome allows for identification of proteins involved in the mechanism of drug action. These attributes make C. elegans well positioned to aid in the discovery of new AD therapies.

Changes in hoof health and animal hygiene in a dairy herd after covering concrete slatted floor with slatted rubber mats: a case study.

The objective was to investigate the effect of changing the flooring in the alleys of a barn from slatted concrete to slatted rubber mats on hoof disorders and animal hygiene in 44 loose-housed Brown Swiss dairy cows. Cows were examined for disorders of the hind hooves (hemorrhages, white line fissures, ulcers, heel horn erosion, and digital dermatitis) and for skin lesions. The dirtiness of the animals and of the floor was recorded. Climatic (temperature, humidity) and ammonia gas conditions were measured. Evaluations were carried out when the cows were housed on a concrete slatted floor and after 4 and 10 mo on soft flooring (slatted rubber mats, 29-mm thick). The anatomical portion of claw (medial, lateral), number of lactations (parity), and days in milk were included as covariates in the statistical model. Changing the flooring from slatted concrete to slatted rubber mats increased the score for white line fissures [1.0 ± 0.3 (concrete) vs. 2.5 ± 0.4 (10 mo rubber mats)] and influenced air humidity (i.e., the difference in the absolute humidity between the inside and outside of the barn increased from 1.5 ± 0.1 to 1.7 ± 0.2g/m(3)), whereas the other hoof disorders, skin lesions (score of 8.7 ± 0.3), the dirtiness of the animals (score of 5.9 ± 0.3), and the floor (score of 2.1 ± 0.1), and ammonia gas concentration (2.6 ± 0.3mg/kg) were not affected (overall scores or measures; mean ± SE). Lateral claws were more affected (except for heel horn erosion) than medial claws (estimated effects between 1.3 ± 0.2 and 3.0 ± 0.6). Parity influenced hoof disorders (except for hemorrhages) and skin lesions (estimated effects between -0.6 ± 0.3 and 0.5 ± 0.2). Days in milk influenced hoof disorders, but had no effect on skin lesions and on the dirtiness of the animal. Irrespective of floor type, the slots (2.6 ± 0.1) were dirtier than the slats (1.6 ± 0.1). In conclusion, covering slatted concrete flooring with slatted rubber mats partially impaired hoof health but did not influence skin lesions or the dirtiness of the cows or the floor. Similar results were found for climatic conditions, as ammonia gas concentration was not affected, but absolute humidity increased in the barn when rubber mats were present.

[Medical decision making in symptoms of type 2 diabetes mellitus in general practice]. / Hausärztliche entscheidungen bei symptomen für diabetes mellitus typ 2.

BACKGROUND: Patient and physician attributes influence medical decisions as non-medical factors. The current study examines the influence of patient age and gender and physicians' gender and years of clinical experience on medical decision making in patients with undiagnosed diabetes type 2. METHOD: A factorial experiment was conducted to estimate the influence of patient and physician attributes. An identical physician patient encounter with a patient presenting with diabetes symptoms was videotaped with varying patient attributes. Professional actors played the "patients". A sample of 64 randomly chosen and stratified (gender and years of experience) primary care physicians was interviewed about the presented videos. RESULTS: Results show few significant differences in diagnostic decisions: Younger patients were asked more frequently about psychosocial problems while with older patients a cancer diagnosis was more often taken into consideration. Female physicians made an earlier second appointment date compared to male physicians. Physicians with more years of professional experience considered more often diabetes as the diagnosis than physicians with less experience. CONCLUSION: Medical decision making in patients with diabetes type 2 is only marginally influenced by patients' and physicians' characteristics under study.

The αGal HyperAcute(®) Technology: enhancing immunogenicity of antiviral vaccines by exploiting the natural αGal-mediated zoonotic blockade.

The αGal HyperAcute(®) Technology exploits a robust zoonotic blockade to enhance potency of antiviral vaccines. Naturally acquired immunity against the common αGal epitope [galactose-alpha(1,3)-galactose-beta(1,4)N-acetylglucosamine-R (Gal-α(1,3)-Gal-ß(1,4)-GlcNAc-R)] is facilitated by the loss of a key enzyme in the epitope's biosynthetic pathway. As human cells are devoid of this epitope, chronic stimulus from gut flora leads to high levels of circulating anti-αGal antibodies and the development of a robust immune pathway. As the αGal epitope is immediately recognized as foreign, the naturally acquired αGal immune pathway in humans serves as a strong barrier to zoonotic infection. The αGal HyperAcute(®) Technology takes advantage of this natural process to facilitate the rapid presentation of modified antigens to antigen-presenting cells, leading to a strong immune response. The evolutionary immunity to αGal ensures that the presence of αGal epitopes on antigens will lead to a robust immune response involving cross-activation of T(H)1 immunity, characterized by cytokine secretion and increased phagocytic activity, and T(H)2 immunity characterized by high antibody titres. αGal epitopes can be applied to antiviral vaccines by biological, enzymatic or chemical means. Several detection methods that directly and indirectly verify αGal addition are discussed. Enhanced immunogenicity (humoral and cellular) of αGal-modified vaccines is shown for several antiviral vaccine candidates. αGal modification of antiviral vaccine components leads to enhanced immunogenicity. The existing body of literature describing the utility of αGal epitopes as a safe and robust immunostimulatory and -modulatory agent in humans supports the basis for applying the αGal HyperAcute(®) Technology to the improvement of antiviral vaccines, both new and currently approved.

[Influence of patient's age and gender on doctors' decision making about coronary heart disease]. / Einfluss von Patientenalter und Patientengeschlecht auf ärztliche Entscheidungen bei koronarer Herzkrankheit.

BACKGROUND: Studies from the United Kingdom und the United States show that there are variations in doctors' decision making regarding coronary heart disease (CHD) and that patient attributes as well as physician characteristics have an impact on medical decisions regardless of the presented symptoms. This study examines how gender and age of patients influence primary care doctors' diagnostic and management decisions regarding CHD in Germany. METHODS: An experimental design with portrayed videotapes is used. Professional actors play the role of patients with symptoms of CHD. Videotapes were identical apart from varying patients' gender and age (55 vs. 75 years). A randomly selected sample of 128 primary care physicians viewed these videotapes in their practices. Afterwards physicians were asked to describe how to diagnose and treat the patient. RESULTS: Women were less likely to be asked about health related behaviours, less likely to get a CHD diagnosis and less likely to be referred to a cardiologist or other specialist. Younger patients were asked about medical history and smoking more frequently, but they were less likely to be asked about symptoms of pain and discomfort. Moreover, among older patients CHD diagnosis was mentioned more often and with higher certainty and medication appropriate for CHD was prescribed more often. DISCUSSION: Age and gender of patients influence primary care doctors' diagnostic and management strategies relating to CHD in Germany regardless of the presented symptoms.

Mineralocorticoid receptor blockade attenuates chronic overexpression of the renin-angiotensin-aldosterone system stimulation of reduced nicotinamide adenine dinucleotide phosphate oxidase and cardiac remodeling.

The renin-angiotensin-aldosterone system contributes to cardiac remodeling, hypertrophy, and left ventricular dysfunction. Angiotensin II and aldosterone (corticosterone in rodents) together generate reactive oxygen species (ROS) via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which likely facilitate this hypertrophy and remodeling. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo mineralocorticoid receptor (MR) blockade in a rodent model of the chronically elevated tissue renin-angiotensin-aldosterone system, the transgenic TG (mRen2) 27 rat (Ren2). The Ren2 overexpresses the mouse renin transgene with resultant hypertension, insulin resistance, proteinuria, and cardiovascular damage. Young (6- to 7-wk-old) male Ren2 and age-matched Sprague-Dawley rats were treated with spironolactone or placebo for 3 wk. Heart tissue ROS, immunohistochemical analysis of 3-nitrotyrosine, and NADPH oxidase (NOX) subunits (gp91(phox) recently renamed NOX2, p22(phox), Rac1, NOX1, and NOX4) were measured. Structural changes were assessed with cine-magnetic resonance imaging, transmission electron microscopy, and light microscopy. Significant increases in Ren2 septal wall thickness (cine-magnetic resonance imaging) were accompanied by perivascular fibrosis, increased mitochondria, and other ultrastructural changes visible by light microscopy and transmission electron microscopy. Although there was no significant reduction in systolic blood pressure, significant improvements were seen with MR blockade on ROS formation and NOX subunits (each P < 0.05). Collectively, these data suggest that MR blockade, independent of systolic blood pressure reduction, improves cardiac oxidative stress-induced structural and functional changes, which are driven, in part, by angiotensin type 1 receptor-mediated increases in NOX.

Sources of variation in physician adherence with clinical guidelines: results from a factorial experiment.

BACKGROUND: Health services research has documented the magnitude of health care variations. Few studies focus on provider level sources of variation in clinical decision making-for example, which primary care providers are likely to follow clinical guidelines, with which types of patient. OBJECTIVES: To estimate: (1) the extent of primary care provider adherence to practice guidelines and the unconfounded influence of (2) patient attributes and (3) physician characteristics on adherence with clinical practice guidelines. DESIGN: In a factorial experiment, primary care providers were shown clinically authentic video vignettes with actors portrayed different "patients" with identical signs of coronary heart disease (CHD). Different types of providers were asked how they would manage the different "patients" with identical CHD symptoms. Measures were taken to protect external validity. RESULTS: Adherence to some guidelines is high (over 50% of physicians would follow a third of the recommended actions), yet there is low adherence to many of them (less than 20% would follow another third). Female patients are less likely than males to receive 4 of 5 types of physical examination (p < .03); older patients are less likely to be advised to stop smoking (p < .03). Race and SES of patients had no effect on provider adherence to guidelines. A physicians' level of experience (age) appears to be important with certain patients. CONCLUSIONS: Physician adherence with guidelines varies with different types of "patient" and with the length of clinical experience. With this evidence it is possible to appropriately target interventions to reduce health care variations by improving physician adherence with clinical guidelines.

Exercise training prevents development of cardiac contractile dysfunction in hypertensive TG (mREN-2)27 rats.

BACKGROUND: Angiotensin-II (Ang-II) contributes to cardiac remodeling and left ventricular dysfunction. In contrast, exercise may have beneficial effects on left ventricular structure and function. METHODS AND RESULTS: We investigated the effects of low-intensity exercise training (ET) on in vivo cardiac function in hypertensive TG (mREN-2)27 rats (Ren-2) which develop left ventricular hypertrophy and dysfunction. Ren-2 rats and Sprague Dawley (SD) controls (4-5 weeks) began treadmill exercise every day for 5-6 weeks. Cardiac function was evaluated by echocardiography. Cardiac output and stroke volume were increased by ET in both 8-wk-old SD and Ren-2. Slope of mitral deceleration time, a non-invasive measure of diastolic function, was lower in the Ren-2 rats, but not changed by ET. LV collagen deposition, as assessed by hydroxyproline assay, was not affected by rat strain or ET at 10-11 weeks of age. Left ventricular B-type natriuretic peptide mRNA levels were higher in the Ren-2 rats (100%), but not affected by ET. Both alpha (~14.5 fold) and beta (~2.5 fold) myosin heavy chain mRNA were higher in the LV of Ren-2 rats (p < 0.05), but were not changed by ET. CONCLUSION: Low-intensity exercise training in Ren-2 rats, a model of Ang-II-mediated hypertension, maintains cardiac index and stroke volume in the presence of impaired diastolic function at 8 wks of age.

Oxidative stress and glomerular filtration barrier injury: role of the renin-angiotensin system in the Ren2 transgenic rat.

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, manifest hypertension, and exhibit increased tissue ANG II levels and oxidative stress. Evidence indicates that elevated tissue ANG II contributes to oxidative stress, increases in glomerular macromolecular permeability, and consequent albuminuria. Furthermore, angiotensin type 1 receptor (AT1R) blockers reduce albuminuria and slow progression of renal disease. However, it is not known whether improvements in glomerular filtration barrier integrity and albuminuria during treatment are related to reductions in oxidative stress and/or kidney renin-angiotensin system (RAS) activity. To investigate the renal protective effects of AT1R blockade, we treated young (6-7 wk old) male Ren2 rats with valsartan (Ren2-V; 30 mg/kg) for 3 wk and measured urine albumin, kidney malondialdehyde (MDA), RAS component mRNAs, and NADPH oxidase subunits (gp91(phox) and Rac1) compared with age-matched untreated Ren2 and Sprague-Dawley (S-D) rats. Basement membrane thickness, slit pore diameter and number, and foot process base width were measured by transmission electron microscopy (TEM). Results indicate that AT1R blockade lowered systolic blood pressure (30%), albuminuria (91%), and kidney MDA (80%) in Ren2-V compared with untreated Ren2 rats. Increased slit pore number and diameter and reductions in basement membrane thickness and podocyte foot process base width were strongly associated with albuminuria and significantly improved following AT1R blockade. AT1R blockade was also associated with increased angiotensin-converting enzyme-2 and neprilysin expression, demonstrating a beneficial shift in balance of renal RAS. Thus reductions in blood pressure, albuminuria, and tissue oxidative stress with AT1R blockade were associated with improved indexes of glomerular filtration barrier integrity and renal RAS in Ren2 rats.

Rat sodium iodide symporter allows using lower dose of 131I for cancer therapy.

Efficient gene delivery is a critical obstacle for gene therapy that must be overcome. Until current limits of gene delivery technology are solved, identification of systems with bystander effects is highly desirable. As an anticancer agent, radioactive iodine (131)I has minimal toxicity. The physical characteristics of (131)I decay allow radiation penetration within a local area causing bystander killing of adjacent cells. Accumulation of (131)I mediated by the sodium iodide symporter (NIS) provides a highly effective treatment for well-differentiated thyroid carcinoma. Other types of cancer could also be treated by NIS-mediated concentration of lethal (131)I radiation in tumor cells. Our group and others previously reported that a significant antitumor effect in mice was achieved after adenoviral delivery of rat or human NIS gene following administration of 3 mCi of (131)I. We have also demonstrated 5-6-fold greater uptake of (125)I by rat NIS over human NIS in human cancer cells. Recently, we reported the capability of the rat NIS and (131)I to effectively induce growth arrest of relatively large tumors (approximately 800 mm(3)) in an animal model. In the present work tumor growth inhibition was achieved using adenoviral delivery of the rat NIS gene and 1 mCi of (131)I (one-third of the dose used in earlier reports). We also demonstrated that a higher concentration of (123)I was accumulated in the NIS-expressing tumors than in the thyroid 20 min after radioiodine administration. The highest intratumoral radioiodine concentration was observed along the needle track; however, the rat NIS-(131)I effectively induced growth arrest of tumor xenografts in mice through its radiological bystander effect. Importantly, the rat NIS allowed reducing the injected radioiodine dose by 70% with the same antitumor efficacy in pre-established tumors. These results suggest that the rat NIS gene may be advantageous compared to the human gene in its ability to enhance intratumoral (131)I uptake.

Invertebrate models of Alzheimer's disease.

The intensely studied model organisms Caenorhabditis elegans and Drosophila melanogaster have been employed to study a number of neurodegenerative diseases, including Alzheimer's disease (AD). Although worms and flies are phylogenetically distant from humans, results of both classic genetic analyses and transgenic manipulation of these invertebrates suggest they are valid models for at least some aspects of AD. This review describes the rationale for AD-relevant studies in worms and flies and discusses both what has been learned from these studies and what may be discovered in the future.

Prevalence of foot and ankle conditions in a multiethnic community sample of older adults.

The prevalence of foot and ankle disorders was determined in a community-based, multiethnic (non-Hispanic White, African American, and Puerto Rican) random sample of 784 community-dwelling adults aged 65 or more years in 2001-2002 in Springfield, Massachusetts. Overall, the five most common conditions were toenail disorders (74.9%), lesser toe deformities (60.0%), corns and calluses (58.2%), bunions (37.1%), and signs of fungal infection, cracks/fissures, or maceration between toes (36.3%); 30.9% had some tenderness to palpation of the foot or ankle, and 14.9% had ankle joint pain on most days in the past 4 weeks. Toenail conditions, fungal symptoms, and ulcers or lacerations were more common in men, while bunions and corns and calluses were more common in women (p < 0.001). Significant racial/ethnic differences, independent of education or gender, were found for the prevalence of most toe deformities and flat feet, as well as for corns and calluses, fungal signs, edema, ankle joint pain, tenderness to palpation, and sensory loss. Foot and ankle disorders are common in these older adults. Examination of their prevalence in different segments of the community may inform future studies to determine etiology and means of prevention.

Functional expression of ATM gene carried by HSV amplicon vector in vitro and in vivo.

Ataxia-telangiectasia (AT) is a human autosomal recessive disease with a pleiotropic phenotype characterized by cerebellar degeneration, immunodeficiency, premature aging, cancer predisposition, and radiation sensitivity. The gene mutated in AT, ATM (for AT-mutated), had been cloned and found to have ionizing radiation and oxidative stress-inducible kinase activity. No treatment can stop the progression of the disease. In this study, the complete open-reading frame of ATM cDNA was cloned into a Herpes simplex virus type-1 (HSV-1) amplicon vector (pTO-ATM), and the transduction of cultured AT cells was demonstrated by immunohistochemistry and Western blot analysis. Functional gene expression was evaluated by cell colony-forming assays following exposure to oxidative stress. The survival of AT cells with ATM gene transduction was about 100% higher compared to nontransduced cells after t-butyl hydroperoxide treatments. Next, the normal ATM gene expression in different regions of the rat brain was studied. Immunohistochemistry staining demonstrated weak endogenous ATM protein expression in neurons of the caudate-putamen, with significantly higher levels of expression detected in neurons in other brain regions. Exogenous ATM gene expression from pTO-ATM after viral transduction in the caudate-putamen of the adult rat was examined. At 3 days after injection of the pTO-ATM viral vector, abundant positive ATM staining of the neurons was found at the injection sites, in comparison to the controls. These data demonstrate that the relatively large ATM cDNA can be transduced and expressed in vitro and in vivo from an HSV amplicon viral vector. These data provide initial evidence that the replacement of the ATM gene into the cells of AT patients might be possible some day.

Transduction of hematopoietic stem cells with a retroviral vector expressing the neomycin phosphotransferase gene.

Transduction of stem cells with a marking gene holds promise to determine if tissue repair or regeneration is derived from the adult hematopoietic stem cell and if relapse of an autoimmune disease should occur whether relapse arises from the stem cell compartment or from lymphocytes surviving the conditioning regimen. New safety concerns about gene-modified stem cell would entail new safety testing such as documentation of the insertional site prior to release.