Predictors of response to pulmonary rehabilitation in stable chronic obstructive pulmonary disease patients: A prospective cohort study.

Context: Pulmonary rehabilitation (PR) has become a standard of care in the management of chronic obstructive pulmonary disease (COPD). However, a significant proportion of the patients do not show benefit after the PR program. Aims: The study was planned to find different patient- and/or disease-related factors that may predict response to PR in stable COPD. Subjects and Methods: A total of 102 stable COPD patients were prospectively enrolled. Baseline evaluation and investigations, including spirometry, arterial blood gas analysis, and bone mineral density assessment, were done. Thereafter, all patients underwent an 8-week comprehensive outpatient PR program that consisted of exercise training, education, nutritional, and psychological counseling. The response to PR was dichotomously (yes/no) defined by the combined improvement in exercise tolerance (6-min walk distance [6MWD] +54 m) and quality of life (St. George's Respiratory Questionnaire [SGRQ] score - 4 points) measured before and after the program. Thereafter, different predefined factors were analyzed for their possible association with the PR response. Results: A total of 80 patients (78.4%) completed the PR program and were subjected for analysis. Out of them, 42 (52.5%) showed improvement in both 6MWD and SGRQ score (46 in 6MWD and 54 in SGRQ score). After application of multivariate logistic regression analysis, forced expiratory volume in 1 s <50% predicted (odds ratio [OR]: 2.9; 95% confidence interval [CI]: 1.1-8.3; P = 0.04) and osteoporosis (OR: 0.26; 95% CI: 0.13-0.53; P < 0.001) were found as independent factors predicting PR efficacy. Conclusions: Poor baseline lung function predicts a short-term improvement in exercise capacity and quality of life in COPD patients, whereas osteoporosis is a negative predictor of PR response. Active search for these factors may help in better patient selection, thus leading to improved outcome after PR.

Gait Speed and Grip Strength Are Associated With Dropping Out of the Liver Transplant Waiting List.

INTRODUCTION: Frailty measures can predict perioperative surgical risk in liver transplant patients. The 5-meter walk test (5MWT) and hand grip strength (HGS) are easy and reproducible frailty measures. We hypothesized that they could capture frailty in liver transplant listed patients and would be associated with dropping out of the waiting list. METHODS: We conducted a retrospective analysis of patients undergoing outpatient liver transplant listing at the University of Pittsburgh Medical Center from 2013 to 2016. We compared demographics, baseline laboratory markers, 5MWT, and HGS between patients who were dropped from the waiting list for medical reasons and those who remained or were successfully transplanted. Bivariate statistical analysis was performed using Fisher exact or χ2 tests. RESULTS: We reviewed 197 patients listed for liver transplant. Average age was 57.1 years (range 20-74), and patients were predominantly white (90.4%). Patients' most common etiology of liver disease was hepatitis C (32.5%), 14 (7.1%) had a previous liver transplant, and average Model for End-Stage Liver Disease score upon listing was 16.0. Of the cohort, 38 (19.3%) were ultimately dropped from the waitlist due to non-hepatocellular carcinoma-related reasons. Patients dropped from the waiting list had weaker HGS (46.14 lb vs 59.6 lb; P < .005) and slower 5MWT speed (5MWT: 0.92 m/s vs 1.03 m/s; P < .005). CONCLUSION: The 5MWT and HGS can easily measure frailty in patients being evaluated for liver transplant. These tests are associated with waiting list dropout, indicating that they can be valuable tools in the evaluation of these patients.

Machinability Investigations of Inconel-800 Super Alloy under Sustainable Cooling Conditions.

With regard to the manufacturing of innovative hard-machining super alloys (i.e., Inconel-800), a potential alternative for improving the process is using a novel cutting fluid approach. Generally, the cutting fluids allow the maintenance of a better tool topography that can generate a superior surface quality of machined material. However, the chemical components of fluids involved in that process may produce harmful effects on human health and can trigger environmental concerns. By decreasing the cutting fluids amount while using sustainable methods (i.e., dry), Near Dry Machining (NDM) will be possible in order to resolve these problems. This paper discusses the features of two innovative techniques for machining an Inconel-800 superalloy by plain turning while considering some critical parameters such as the cutting force, surface characteristics (Ra), the tool wear rate, and chip morphology. The research findings highlight the near-dry machining process robustness over the dry machining routine while its great potential to resolve the heat transfer concerns in this manufacturing method was demonstrated. The results confirm other benefits of these methods (i.e., NDM) linked to the sustainability aspects in terms of the clean process, friendly environment, and permits as well as in terms of improving the manufacturing characteristics.

Preovulatory follicle characteristics and oocyte competence in repeat breeder dairy cows.

The varied and elusive etiology of repeat breeding (RB) in dairy cows necessitates evaluation of oocytes and follicles, which have not previously been assessed together. Accordingly, we evaluated characteristics of preovulatory follicles and the competence of oocytes in control (CTL) and RB cows. The estrous cycles of 35 cows (18 CTL and 17 RB) were synchronized using PGF2α and estrus detection. Cows with a corpus luteum were treated with PGF2α and, 14 to 15 d after a visible behavioral estrus, they were administered a second PGF2α, followed 48 h later by follicular fluid (FF) aspiration of the preovulatory follicles. Estradiol (E2)-active preovulatory follicles did not differ in diameter between the 2 groups of cows. However, FF of RB cows had higher E2 concentrations than that of CTL cows: 1,854.9 and 1,073.6 ng/mL, respectively, but similar androstenedione and progesterone concentrations. In the second part of the study, 14 consecutive ovum pick-ups (OPU) were performed in 5 CTL and 5 RB cows, at 3- to 4-d intervals. The RB and CTL cows did not differ in average numbers of follicles available per cow per session (7.1 and 7.3, respectively), oocyte recovery rates (42.2 and 44.1%, respectively), or cleavage rates (57.6 and 63.4%, respectively), but blastocyst production was markedly less in RB than in CTL cows (12.5 and 29.2%, respectively). We conclude that part of the RB cows' etiology occurs at an earlier phase of folliculogenesis, thereby impairing oocyte competence, and subsequently reducing the probability of normal fertilization, which diminish embryo vitality and development.

Sexual dysfunction and central obesity in patients with first episode psychosis.

BACKGROUND: In recent years the association between sexual dysfunction (SD) and obesity in the general population has drawn major attention. Although sexual dysfunction is common in psychosis, its relationship with weight gain and obesity remains unclear. AIMS: To investigate the association between sexual dysfunction and obesity in a cohort of patients with first episode psychosis. METHOD: Sexual function was assessed in a cohort of patients with first episode psychosis using the Sexual Function Questionnaire (SFQ). Anthropometric measures, including weight, BMI, waist, waist-hip ratio were investigated. Additionally, leptin and testosterone were investigated in male patients. RESULTS: A total of 116 patients (61 males and 55 females) were included. Of these 59% of males and 67.3% of females showed sexual dysfunction (SD) according to the SFQ. In males, higher SFQ scores were significantly correlated with higher BMI (Std. ß=0.36, P=0.01), higher leptin levels (Std. ß=0.34, P=0.02), higher waist-hip ratio (Std. ß=0.32, P=0.04) and lower testosterone levels (Std. ß=-0.44, P=0.002). In contrast, in females, SFQ scores were not associated with any of these factors. CONCLUSIONS: While sexual dysfunction is present in both female and male patients with their first episode of psychosis, only in males is sexual dysfunction associated with increased BMI and waist-hip ratio. The association between SD, BMI, low levels of testosterone and high levels of leptin suggest that policies that lead to healthier diets and more active lifestyles can be beneficial at least, to male patients.

Clinical correlates of vitamin D deficiency in established psychosis.

BACKGROUND: Suboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis. METHODS: Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and "sufficient" Vitamin D as above 30 ng/ml (>50 nmol/L). RESULTS: The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14 % (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = -0.220, p < 0.002), triglycerides (r = -0.160, p = 0.024), total cholesterol (r = -0.144, p = 0.043), fasting glucose (r = -0.191, p = 0.007), HbA1c (r = -0.183, p = 0.01), and serum CRP levels (r = -0.211, p = 0.003) and were linked to the presence of metabolic syndrome. CONCLUSIONS: This is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk. TRIAL REGISTRATION: ISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010.

Impact of childhood adversities on specific symptom dimensions in first-episode psychosis.

BACKGROUND: The relationship between childhood adversity (CA) and psychotic disorder is well documented. As the adequacy of the current categorical diagnosis of psychosis is being increasingly questioned, we explored independent associations between different types of CA and specific psychotic symptom dimensions in a well-characterized sample of first-episode psychosis (FEP) patients. METHOD: This study involved 236 FEP cases aged 18-65 years who presented for the first time to psychiatric services in South London, UK. Psychopathology was assessed with the Positive and Negative Syndrome Scale and confirmatory factor analysis was used to evaluate the statistical fit of the Wallwork/Fortgang five-factor model of psychosis. CA prior to 17 years of age (physical abuse, sexual abuse, parental separation, parental death, and being taken into care) was retrospectively assessed using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Childhood sexual abuse [ß = 0.96, 95% confidence interval (CI) 0.40-1.52], childhood physical abuse (ß = 0.48, 95% CI 0.03-0.93) and parental separation (ß = 0.60, 95% CI 0.10-1.11) showed significant associations with the positive dimension; while being taken into care was associated with the excited dimension (ß = 0.36, 95% CI 0.08-0.65), independent of the other types of CA. No significant associations were found between parental death and any of the symptom dimensions. CONCLUSIONS: A degree of specificity was found in the relationships between different types of CA and psychosis symptom dimensions in adulthood, suggesting that distinct pathways may be involved in the CA-psychosis association. These potentially different routes to developing psychosis merit further empirical and theoretical exploration.

Association of Amelogenin with High Caries Experience in Indian Children.

OBJECTIVE: The purpose of this study was to identify alterations in amelogenin gene that are associated with dental caries susceptibility and to develop a non-invasive early screening test for caries risk. STUDY DESIGN: 60 individuals were selected for the study based on the inclusion and exclusion criteria and were divided into two groups based on DMFT score. DMFT was scored according to World Health Organization guidelines. Saliva obtained from all participants was stored in Indogenix DNA Self-Collection kits at 4°C. DNA was extracted according to the manufacturer's instructions. Once the entire DNA was isolated from each sample it was put forward for PCR amplification. The amplified amelogenin gene was then run on 2% agarose gel stained with ethidium bromide. The amplified gene was processed by SSCP technique to find out the altered bands and then subjected to DNA sequencing for identification of alterations in the amino acid sequence of amelogenin gene. RESULTS: The sequencing data showed the presence of mutation. Samples showing mutation (43.3%) showed high correlation with caries (80.7%) experience which was statistically significant. CONCLUSION: Understanding the genetics of dental caries susceptibility will provide new insights into the caries process in individuals and will facilitate the development of targeted preventive strategies.

Comparative Study of Pulp Vitality in Primary and Young Permanent Molars in Human Children with Pulse Oximeter and Electric Pulp Tester.

AIM AND OBJECTIVE: The purpose of this study was to compare the pulp testing methods (pulse oximetry and electric pulp test) in primary and young permanent teeth of children. MATERIALS AND METHODS: The study included a total of 155 children aged 4 to 15 years. Twenty children formed control group I. Study group included all healthy, 85 primary 2nd molars in group II and 85 permanent 1st molars in group III. Fifty children needing endodontics treatment formed test group IV. The readings were recorded as true positive (TP), false positive (FP), true negative (TN), false negative (FN). Based on this, the sensitivity, specificity, positive predictive value and negative predictive value were calculated for each method. The results were statistically analyzed using Chi-square test. RESULTS: On comparing pulse oximetry with electric pulp test 'p-value' was found to be 0.487 and 1.00 for groups 1 and 2 respectively and was statistically not significant. Whereas 'p-value' for groups 3 and 4 was < 0.0001 and 0.003 respectively and was statistically highly significant. CONCLUSION: The present study indicates that pulse oximetry can be used as a routine method for assessing the pulp vitality in primary, young permanent and mature permanent teeth. How to cite this article: Shahi P, Sood PB, Sharma A, Madan M, Shahi N, Gandhi G. Comparative Study of Pulp Vitality in Primary and Young Permanent Molars in Human Children with Pulse Oximeter and Electric Pulp Tester. Int J Clin Pediatr Dent 2015;8(2):94-98.

Saliva as a prediction tool for dental caries: An in vivo study.

INTRODUCTION: The present study was undertaken to assess the caries activity by comparing the pH, buffering capacity, calcium, phosphorous, amylase along with the association of mutans in saliva for caries-free and caries-active children and to find out the interrelationship amongst the two groups. METHODOLOGY: The study sample of 80 children, aged between 4 and 8 years were included in the study. Caries status of each child was recorded using DMFS. They were divided into two groups: (i) caries-free group (40) and (ii) caries-active group (40). After collecting the salivary samples, mutans were determined using Saliva-Check mutans kit and buffering capacity by Saliva-Check Buffer kit. The remaining samples were sent to laboratory for analyzing pH by electrode pH meter, calcium by OCPC(o-cresolphthalein complexone) photometric method, phosphorous by phosphomolybdate/UV method, amylase by CNP-G3(2chloro-4-nitrophenyl-alpha-maltotrioside) method using semi-autoanalyzer. RESULTS: The results obtained were tabulated and subjected to statistical analysis. The pH, buffering capacity, calcium and phosphorous level were found to be increased with the decrease in the caries activity of the children whereas amylase activity was increased with the increase in caries activity. It was observed that 77.5% children were tested positive and 22.5% were tested negative for mutans in caries-active group whereas 100% children were tested negative for mutans in caries-free group. CONCLUSION: The physicochemical properties of saliva, such as pH, buffering capacity, calcium, phosphorous, amylase and Streptococcus mutans has a definite relationship with caries activity.

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: baseline data from the IMPaCT RCT study--Corrigendum.

The author regrets to announce that affiliation 8, in the above article (Gardner-Sood et al. 2015), contained an error in the author affiliation address and author surname, which were published in the approved article. The correct surname and affiliation address are given below. J. Eberhard, Clinical Psychiatric Research Center, Lund University, Skåne, Sweden

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: baseline data from the IMPaCT randomized controlled trial.

BACKGROUND: The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment. METHOD: Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18-65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria. RESULTS: High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS. CONCLUSIONS: In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.

Commercially available immunoglobulins contain virus neutralizing antibodies against all major genotypes of polyomavirus BK.

Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.

Behavioral and hormonal pattern of repeat breeder cows around estrus.

Repeat breeder (RB) cows were compared with normal (CTRL) ones with respect to behavioral estrus intensity, endocrine patterns and concentrations of plasma estradiol, progesterone and LH around estrus, and ovulation timing. A total of 27 and 31 cycles in 12 RB and 18 CTRL cows, respectively, were synchronized by means of the Ovsynch protocol followed by a single PG injection after 7 days. Behavioral estrus and ovulation were observed in 81.5 and 83.8% of the synchronized cycles in the RB and CTRL cows respectively. The RB and CTRL groups had similar estrus durations of 21.4 and 19.6 h respectively, but estrus was more intense in the RB, as indicated by numerically higher overall activity indexes and higher peak neck activity. The interval from PG injection to estrus onset (considered as proestrus) was 8.2 h shorter in RB than in CTRL cows, at 47.9 and 56.1 h respectively (P<0.007), but the average preovulatory follicle size was similar. The estradiol concentration at peak was numerically higher (21%) and the AUC tended to be higher in the RB cows than in the CTRL cows. LH secretion during the period from 18 to 3 h before the LH peak was also lower in RB than in CTRL cows: 2.5 and 4.6 ng/ml respectively (P<0.01). In conclusion, the behavioral estrus was more intense in the RB cows; nevertheless, short proestrus and subdued LH concentrations before the LH peak, which could impair oocyte competence and development, were first reported in RB cows.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the rapid identification of yeasts causing bloodstream infections.

Few studies have systematically standardised and evaluated matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of yeasts from bloodstream infections. This is rapidly becoming pertinent for early identification of yeasts and appropriate antifungal therapy. We used 354 yeast strains identified by polymerase chain reaction (PCR) sequencing for standardisation and 367 blind clinical strains for validation of our MALDI-TOF MS protocols. We also evaluated different sample preparation methods and found the on-plate formic acid extraction method as most cost- and time-efficient. The MALDI-TOF assay correctly identified 98.9% of PCR-sequenced yeasts. Novel main spectrum projections (MSP) were developed for Candida auris, C. viswanathii and Kodamaea ohmeri, which were missing from the Bruker MALDI-TOF MS database. Spectral cut-offs computed by receiver operating characteristics (ROC) analysis showed 99.4% to 100% accuracy at a log score of ≥ 1.70 for C. tropicalis, C. parapsilosis, C. pelliculosa, C. orthopsilosis, C. albicans, C. rugosa, C. guilliermondii, C. lipolytica, C. metapsilosis, C. nivariensis. The differences in the species-specific scores of our standardisation and blind validation strains were not statistically significant, implying the optimal performance of our test protocol. The MSPs of the three new species also were validated. We conclude that MALDI-TOF MS is a rapid, accurate and reliable tool for identification of bloodstream yeasts. With proper standardisation, validation and regular database expansion, its efficiency can be further enhanced.

A comparative clinical study of various methods of caries removal in children.

AIM: The aim of the study was to compare the efficacy of caries removal, time taken and to evaluate the pain threshold experienced by children during various caries removal methods. METHODS: One hundred and twenty patients aged between 4 and 14 years requiring dental restorations were selected. Caries removal was completed using an air-rotor, hand instruments, Carisolv and polymer burs. The efficacy, time taken and pain thresholds were evaluated during caries removal by Ericsson et al. scale, visual analogue scale and verbal pain scale, respectively. STATISTICAL ANALYSIS: Data was collected and statistically analysed using one-way analysis of variance followed by Post Hoc comparison by Bonferroni method. The skewed data was analysed amongst groups by applying Kruskal-Wallis test followed by probability adjustment by Mann-Whitney test. RESULT: These results indicated that the efficacy of caries removal was highest with air-rotor and was least by the hand instrument, whilst Carisolv® was least painful and the most time-consuming method. CONCLUSIONS: Caries removal with polymer burs and Carisolv were found to be as effective in caries removal and could be considered as alternatives to painful procedures as air-rotor in management of caries especially in children.

Provision of health promotion programmes to people with serious mental illness: a mapping exercise of four South London boroughs.

BACKGROUND: People with serious mental illness (SMI) are at increased risk of developing various physical health diseases, contributing to significantly reduced life expectancies compared with the general population. In light of this, the Department of Health have set the physical health of people with mental health problems as a priority for improvement. Additionally, the UK government encourages the NHS and local authorities to develop health promotion programmes (HPPs) for people with SMI. AIMS: To document how many and what types of HPPs were available to people with SMI across four South London boroughs, UK. RESULTS: We found 145 HPPs were available to people with SMI across the four boroughs, but with an inequitable distribution. We also found that certain HPPs set admission criteria that were likely to act as a barrier to improving health. CONCLUSIONS: A more integrated approach of documenting and providing information regarding the provision of HPPs for or inclusive of people with SMI is needed. ABSTRACT: People with serious mental illness (SMI) such as schizophrenia, schizoaffective disorders and bipolar disorder are at increased risk of developing diabetes, cardiovascular disease and respiratory disease, contributing to significantly reduced life expectancies. As a result, emphasis has been placed on developing Health Promotion Programmes (HPPs) to modify the risk of poor physical health in SMI. We examined how many and what types of HPPs are available for or inclusive of people with SMI across four borough in South London, UK. A cross-sectional mapping study was carried out to identify the number of HPPs available to people with SMI. We found 145 HPPs available to people with SMI existed across the four boroughs but with an inequitable distribution, which in some boroughs we anticipate may not meet need. In some cases, HPPs set admission conditions which were likely to further impede access. We recommend that accurate and readily available information on the provision of HPPs for or inclusive of people with SMI is needed.

Management of a rare case of impacted primary central incisors in a 3-year-old child.

Impaction of primary anterior teeth is very rare. A tooth that fails to erupt into normal functional position by the time it normally should is considered impacted. A rare case of impacted dilacerated maxillary primary incisors in a 3-year-old child is presented. The diagnostic position of impacted primary incisors was determined using conical beam computed tomography (CBCT) to assist in surgical intervention with least surgical trauma to the tissues.

Role of killer immunoglobulin-like receptor-ligand interactions in human leukocyte antigen-matched sibling hematopoietic stem cell transplantation.

INTRODUCTION: Killer immunoglobulin-like receptor (KIR)-ligand mismatches lead to natural killer cell alloreactivity after hematopoietic stem cell transplantation (HSCT). However, their clinical impact on HSCT outcomes is controversial due to complexity of KIR haplotypes, genotypes, and phenotypes as well as their diversity among patient populations. The present study investigated the role of KIR-ligand interactions in human leukocyte antigen (HLA)-matched sibling transplants. METHODS: The recipient cohort, which included patients diagnosed with aplastic anemia, acute leukemia, and myelodysplastic syndrome, received granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells. HLA typing was performed using polymerase chain reaction - sequence specific oligo probes (PCR-SSO). The KIR genotype of the donors and the ligands C1 (Asparagine 80), C2 (Lysine 80), and Bw4 recipient typings were performed using polymerase chain reaction - sequence specific primers (PCR-SSP). We assessed acute and chronic graft-versus-host disease (GVHD), relapse, and overall survival. RESULTS: While 84.5% of donors carried a Bx KIR, 15.5% carried the AA haplotype. The effect of a recipient's lack of ligands among 88.5% of cases was associated with 39% of subjects developing GvHD. Lack of C1 may lead to manifestations of acute GvHD and lack of C2 to manifestation of chronic GvHD. The presence of both C1 and C2 seemed to be protective against both forms of GvHD. The role of two Bw4 alleles, threonine (T) or isoleucine (I) at position 80, was evaluated. 73% of recipients who carried Bw4 80(I) versus 27% with the Bw4 80(T) allele. The presence of Bw4-80(T) allele appeared to reduce the risk of GvHD, indicating its stronger inhibitory effect than its 80(I) counterpart. CONCLUSION: KIR-ligand interactions influenced HSCT outcomes.

Audit of peripheral stem cell transplantation for aplastic anemia in multitransfused infected patients.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation is a curative modality for aplastic anemia; the preferred stem cell source is bone marrow. However, allogeneic peripheral blood stem cell transplantation (PBSCT) used in high-risk patients is associated with higher risk of chronic graft-versus-host disease (GVHD). Our center receives multitransfused, alloimmunized, infected, late referrals for transplant. METHODS: Forty-one patients of median age 22 years (range 8-37) received allogeneic-PBSCT from human leukocyte antigen (HLA)-matched sibling donors. The median time since diagnosis was 12 months (range 4-65) and median pretransplant transfusions were 37 (range 6-160). Six patients were platelet refractory and one alloimmunized for pan-red blood cell (RBC) antigens. Several patients had pretransplant icterus or renal dysfunction and 26 (63.4%) had unresponsive bacterial/fungal infections. Our conditioning regimen included fludarabine 30 mg/m(2) for 6 days (days -10 to -5), cyclophosphamide 60 mg/kg/d for 2 days (days -6 to -5), and antithymocyte globulin (ATGAM) 30 mg/kg/d for 4 days (day -4 to -1), which was reduced to 2 days in 2 patients. We used standard GVHD prophylaxis with cyclosporine and methotrexate on days 1, 3, 6, 11. RESULTS: The median follow-up period was 29 months (range 6-78) and median engraftment time 10 days (range 8-17). Thirty-one patients (75.6%) were treated for infections, with 20 of these on antifungals for preexisting infections. There were two graft rejections and 10 (24.4%) deaths, with three intracranial hemorrhages, two rejections with infection, three cases of refractory GVHD (acute/overlap syndrome) with cytomegalovirus reactivation, and two invasive fungal infections. Overall incidence of acute GVHD was 39% with 2 grade IV cases. Ten (25%) cases developed chronic GVHD, with extensive GVHD in four. CONCLUSION: With more experience using shortened course of ATGAM, HLA-matched donor transfusions, and availability of newer antifungals, we have been able to decrease PBSCT-related mortality. Further improvement will be possible with early referrals.