B subgroup detection in a small hospital transfusion service.

The ABO blood group system includes phenotypes, or subgroups, that differ in the amount of A and B antigens present on the red blood cells (RBCs). These subgroups also differ in the A, B, or H substances present in secretions (for individuals who have the secretor phenotype). B subgroups are very rare and are less frequently reported than A subgroups. Usually, B subgroups are discovered during serologic testing when there is a discrepancy between RBC and serum grouping results. Subgroups of B are usually identified by a reference laboratory using molecular and adsorption-elution methods. This report details a case of a young, healthy, pregnant woman with a B subgroup detected by a small transfusion service using adsorption-elution methods. Serology and genotyping of the ABO gene was performed at a reference laboratory where the serology was consistent with a B subgroup, but no changes were identified in ABO gene sequencing. It is important to correctly identify B subgroups in donors and recipients to help resolve ABO discrepancies and potentially prevent ABO incompatibility in blood transfusion, thus minimizing transfusion reactions.The ABO blood group system includes phenotypes, or subgroups, that differ in the amount of A and B antigens present on the red blood cells (RBCs). These subgroups also differ in the A, B, or H substances present in secretions (for individuals who have the secretor phenotype). B subgroups are very rare and are less frequently reported than A subgroups. Usually, B subgroups are discovered during serologic testing when there is a discrepancy between RBC and serum grouping results. Subgroups of B are usually identified by a reference laboratory using molecular and adsorption-elution methods. This report details a case of a young, healthy, pregnant woman with a B subgroup detected by a small transfusion service using adsorption-elution methods. Serology and genotyping of the ABO gene was performed at a reference laboratory where the serology was consistent with a B subgroup, but no changes were identified in ABO gene sequencing. It is important to correctly identify B subgroups in donors and recipients to help resolve ABO discrepancies and potentially prevent ABO incompatibility in blood transfusion, thus minimizing transfusion reactions.

Clozapine administration in clinical practice: once-daily versus divided dosing.

OBJECTIVE: While it is recommended that clozapine be administered in a divided dosing regimen, it is unclear whether this recommendation is followed in real-world clinical practice. In two large datasets, we examined clozapine dosing frequency and patient characteristics across different dosing regimens. METHOD: We conducted a cross-sectional survey, collecting data on patients receiving clozapine in August/September 2015 from the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada, and The Zucker Hillside Hospital (ZHH) in New York, United States. RESULTS: Of 676 and 308 patients included in CAMH and ZHH datasets, clozapine was prescribed once daily in 75.1% and 74.4%, even though doses exceeding 200 mg/day were administered in 88.6% and 84.4% of the respective samples. No significant difference was found in the rates of positive symptom remission between once-daily vs. divided dosing (79.7% vs. 80.5%, P = 1.00). Higher clozapine dose and use of anticholinergic medications were significantly associated with divided dosing in both datasets. Older age or male gender was related to divided dosing in CAMH or ZHH dataset respectively. CONCLUSION: Despite the product monograph recommendation, clozapine is frequently prescribed once daily in North America. Further studies are needed to compare clinical outcomes between once-daily vs. divided clozapine dosing.

Clozapine's critical role in treatment resistant schizophrenia: ensuring both safety and use.

INTRODUCTION: Clozapine was first introduced as an antipsychotic in the 1970's but a cluster of deaths, later linked to the drug's risk of agranulocytosis, led to its withdrawal in most countries. However, work in the 1980's established its unique efficacy in treatment resistant schizophrenia (TRS), which constitutes as many as 30% of those with the illness. Clozapine was reintroduced with this indication shortly thereafter, but because of this risk its use requires routine hematologic monitoring. AREAS COVERED: An update is provided regarding clozapine's risk of neutropenia, agranulocytosis, and associated mortality. In addition, updates are provided on other side effects, specifically myocarditis and bowel obstruction, as evidence suggests these are more common than agranulocytosis and associated with higher mortality rates. EXPERT OPINION: Clozapine remains the only treatment indicated in TRS, but it is dramatically underutilized. Clearly there are serious side effects associated with its use, and while the focus has historically been on hematologic concerns, we highlight other side effects that also demand systematic monitoring. Because it is the only effective treatment option we have for TRS, though, efforts must be implemented that ensure its use in this population while maximizing safety.

Comparison of the measurement of heart rate in adult free-range chickens (Gallus domesticus) by auscultation and electrocardiography.

OBJECTIVE: To compare the heart rates of adult free-range chickens (Gallus domesticus) measured by auscultation with a stethoscope with those measured simultaneously using electrocardiography (ECG). METHODS: With each bird in a standing position, estimation of the heart rate was performed by placing a mark on paper for every 4 beats for roosters and 8 beats for hens as detected by auscultation over 30 s, while simultaneous ECG was performed. RESULTS: Heart rates measured by auscultation showed a high correlation (r = 0.97) with those measured by ECG. CONCLUSION: There was a high correlation between the heart rates of adult free-range chickens measured by auscultation with a stethoscope and those measured simultaneously using ECG.

Efficacy of the trial-based thought record, a new cognitive therapy strategy designed to change core beliefs, in social phobia.

WHAT IS KNOWN AND BACKGROUND: Social anxiety disorder (SAD) often follows a chronic course and is associated with substantial impairment in functioning. Although results from clinical trials clearly establish evidence for efficacy of cognitive behavioural therapy in treating this disorder, up to 50% of patients with SAD show little or no improvement. Thus, new approaches that have promised in improving the efficacy of treatment for SAD are needed. One such approach is the trial-based thought record (TBTR), which targets the restructuring of patients' core beliefs. OBJECTIVE: To determine whether patients receiving TBTR would report fewer symptoms of social anxiety and general psychiatric distress following treatment, relative to conventional cognitive therapy (CCT). METHODS: A two-arm randomized trial comparing TBTR (n = 17) with a set of CCT techniques (n = 19), which included the standard seven-column dysfunctional thought record and the positive data log in SAD patients according to DSM-IV. RESULTS: Scores on many outcome measures decreased significantly across the course of treatment in both groups (P < 0·001), including the Liebowitz Social Anxiety Scale, Fear of Negative Evaluation Scale (FNE), Social Avoidance and Distress Scale (SADS), Beck Anxiety Inventory, and Clinical Global Impression - Improvement. In addition, a one-way ancova, taking baseline values as covariates, showed that TBTR was significantly more efficacious than CCT in reducing the scores of FNE (P = 0·01 at mid-treatment and P = 0·004 at post-treatment), and SADS (P = 0·03 at post-treatment). WHAT IS NEW AND CONCLUSION: This study provides preliminary evidence that TBTR is at least as efficacious as CCT in reducing symptoms of SAD, pointing to the need for additional studies of TBTR in SAD and other psychiatric disorders.

The effect of speed-accuracy strategy on response interference control in Parkinson's disease.

Studies that used conflict paradigms such as the Eriksen Flanker task show that many individuals with Parkinson's disease (PD) have pronounced difficulty resolving the conflict that arises from the simultaneous activation of mutually exclusive responses. This finding fits well with contemporary views that postulate a key role for the basal ganglia in action selection. The present experiment aims to specify the cognitive processes that underlie action selection deficits among PD patients in the context of variations in speed-accuracy strategy. PD patients (n=28) and healthy controls (n=17) performed an arrow version of the flanker task under task instructions that either emphasized speed or accuracy of responses. Reaction time (RT) and accuracy rates decreased with speed compared to accuracy instructions, although to a lesser extent for the PD group. Differences in flanker interference effects among PD and healthy controls depended on speed-accuracy strategy. Compared to the healthy controls, PD patients showed larger flanker interference effects under speed stress. RT distribution analyses suggested that PD patients have greater difficulty suppressing incorrect response activation when pressing for speed. These initial findings point to an important interaction between strategic and computational aspects of interference control in accounting for cognitive impairments of PD. The results are also compatible with recent brain imaging studies that demonstrate basal ganglia activity to co-vary with speed-accuracy adjustments.

The effect of Parkinson's disease on interference control during action selection.

Basal ganglia structures comprise a portion of the neural circuitry that is hypothesized to coordinate the selection and suppression of competing responses. Parkinson's disease (PD) may produce a dysfunction in these structures that alters this capacity, making it difficult for patients with PD to suppress interference arising from the automatic activation of salient or overlearned responses. Empirical observations thus far have confirmed this assumption in some studies, but not in others, due presumably to considerable inter-individual variability among PD patients. In an attempt to help resolve this controversy, we measured the performance of 50 PD patients and 25 healthy controls on an arrow version of the Eriksen flanker task in which participants were required to select a response based on the direction of a target arrow that was flanked by arrows pointing in the same (congruent) or opposite (incongruent) direction. Consistent with previous findings, reaction time (RT) increased with incongruent flankers compared to congruent or neutral flankers, and this cost of incongruence was greater among PD patients. Two novel findings are reported. First, distributional analyses, guided by dual-process models of conflict effects and the activation-suppression hypothesis, revealed that PD patients are less efficient at suppressing the activation of conflicting responses, even when matched to healthy controls on RT in a neutral condition. Second, this reduced efficiency was apparent in half of the PD patients, whereas the remaining patients were as efficient as healthy controls. These findings suggest that although poor suppression of conflicting responses is an important feature of PD, it is not evident in all medicated patients.

Using NVDRS data for suicide prevention: promising practices in seven states.

OBJECTIVES: This article describes how seven states participating in a new public health surveillance system for violent death in the US, the National Violent Death Reporting System (NVDRS), have used data to support local suicide prevention activities. SETTING: The NVDRS is unique in that it augments death certificate data with event and circumstance information from death investigation reports filed by coroners, medical examiners, and law enforcement. These data illuminate why the victim ended his or her life, fatal injury patterns, and toxicological findings at death. RESULTS: Current suicide prevention efforts using these data fall into three categories: describing the problem of suicide and identifying opportunities for intervention; collaborating on statewide suicide prevention plans; and forming new partnerships for targeted prevention initiatives. Taken together, these three areas show early promise for state suicide prevention efforts. CONCLUSIONS: In each of the states, NVDRS data analyses are being shared with injury prevention colleagues, suicide prevention planning groups and policymakers, and adapted to respond to unique state and local suicide problems. A powerful surveillance tool, the NVDRS is bringing new clarity and direction to these state-based efforts. The NVDRS can serve as a model for other countries looking to establish timely suicide surveillance systems and data driven prevention strategies.

From surveillance to action: early gains from the National Violent Death Reporting System.

OBJECTIVES: Drawing from the experiences of individual state programs that currently participate in the National Violent Death Reporting System (NVDRS), this article reviews some of the practical benefits that may accrue from the introduction of violent death surveillance systems. DESIGN: As a state-based surveillance system that uses multiple data sources and relies upon multiple stakeholders, the NVDRS program has fostered an array of initiatives within and among individual state programs. State-based initiatives highlighted in this article were selected on the basis of a purposive sampling strategy intended to illustrate key aspects of program development. SETTING: The NVDRS state programs are in Alaska, California, Colorado, Georgia, Kentucky, Maryland, Massachusetts, New Jersey, New Mexico, North Carolina, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Virginia, and Wisconsin. RESULTS: The NVDRS has helped to build alliances and collaborative efforts between key stakeholders, facilitated the recognition of violent death as a public health problem through outreach and media attention, acted as a catalyst for new projects, enhanced surveillance of special populations and utility for evaluation, and identified key circumstances that will target interventions in state prevention planning. CONCLUSIONS: The NVDRS has implemented data collection efforts and is beginning to produce and analyze findings. In the process of implementing the data collection system and publicizing findings, state NVDRS programs are realizing other gains that strengthen their surveillance efforts. The use of data for prevention purposes will be the ultimate indicator of program success.

Rhnull syndrome: identification of a novel mutation in RHce.

BACKGROUND: The deficiency of Rh proteins on red blood cells (RBCs) from individuals of the Rh(null) amorph type are the result of homozygosity for a silent RHCE in cis with a deleted RHD. A novel mutation in RHce was identified in two Caucasian Brazilian girls with the amorph type of Rh(null) who were born to parents who were first cousins. STUDY DESIGN AND METHODS: RBCs from the Rh(null) sisters and from family members were analyzed by serology and flow cytometry with specific antibodies. Genomic DNA and transcripts were tested by polymerase chain reaction and sequence analysis. RESULTS: Rh(null) RBCs were nonreactive with anti-Rh and anti-LW. Molecular analyses showed a deletion of RHD and of one nucleotide (960/963; GGGG-->GGG) in exon 7 of the RHce. This deletion introduced a frameshift after Gly321, a new C-terminal sequence, and a premature stop codon, resulting in a shorter predicted protein with 357 amino acids. CONCLUSION: The detection of a unique RHce transcript indicated that the two sisters were homozygous, whereas the other family members were heterozygous for the mutation. A novel mutation resulting in the amorph Rh(null) with loss of Rh antigen expression is described.

Novel molecular basis of an Inab phenotype.

The Cromer blood group system consists of ten high-prevalence and three low-prevalence antigens carried on decay-accelerating factor (DAF). DAF is found in the cell membranes of RBCs, granulocytes, platelets, and lymphocytes and is widely represented in other body tissues. Sequence analyses of DNA were performed on a blood sample from a 91-year-old Japanese woman whose serum contained an alloantibody to a high-prevalence antigen in the Cromer blood group system (anti-IFC). A blood sample from her daughter was also studied. Sequence analysis revealed a substitution of 508C7>T in exon 4 of DAF in the proband. The proband's daughter was heterozygous for 508C/T. This study describes an Inab phenotype in which the 508C>T nonsense mutation is predicted to change arginine at amino acid residue 136 to a stop codon. This change is in SCR 3 of DAF. This study reports on the molecular basis of a new proband with the Inab phenotype who had no history of intestinal disorders.

RH locus contraction in a novel Dc-/D-- genotype resulting from separate genetic recombination events.

BACKGROUND: The rare phenotypes Dc- and D-- lack the expression of E/e and CcEe antigens, respectively; their cotransmission in a single family has not been reported. STUDY DESIGN AND METHODS: Six members of a Chinese family with two exhibiting the Dc- phenotype were studied using standard serologic methods. Rh genotypes were analyzed by Southern blot, and RH loci, by exon PCR. Rh transcripts were characterized by gene-specific RT-PCR and sequencing. RESULTS: Although Rh typing detected two members as Dc- homozygotes, RFLP analysis and exon PCR showed them to be Dc- heterozygotes with a partial deletion of RHCE. cDNA sequencing showed the expression in the family of normal RHD and RHCe as well as hybrid transcripts, RHD(1-9)/RHCE(10) and RHCE(1-3)/RHD(4-10). Thus, the Dc- members had the genotype of Dc-/ D-- and expressed both hybrid genes that were inherited from their parents, respectively. DISCUSSION: This is the first demonstration in a family that the Dc- and D-- complexes neither are linked with a normal RHD or RHCE gene. The segregation of these two different hybrid genes with single break points suggests their independent genetic origin and provides molecular insights into the dynamic nature of genomic rearrangements leading to RH locus contraction.

Assessment of periodontal conditions and systemic disease in older subjects. II. Focus on cardiovascular diseases.

BACKGROUND: Panoramic radiographs (PMX)s may provide information about systemic health conditions. AIMS: i). To study clinical periodontal conditions and collect self-reported health status in a cohort of 1084 older subjects; ii). to study signs of alveolar bone loss and carotid calcification from panoramic radiographs obtained from these subjects; and iii). to study associations between study parameters. MATERIAL AND METHODS: PMXs from 1064 adults aged 60-75 (mean age 67.6, SD +/- 4.7) were studied. Signs of alveolar bone loss, vertical defects, and molar furcation radiolucencies defined periodontal status. Medical health histories were obtained via self-reports. Signs of carotid calcification were identified from panoramic radiographs. RESULTS: The PMX allowed assessment of 53% of the films (Seattle 64.5% and Vancouver 48.4%). A self-reported history of a stroke was reported by 8.1% of men in Seattle and 2.9% of men in Vancouver (P < 0.01). Heart attacks were reported by 12% of men in Seattle and 7.2% in Vancouver (N.S.). PMX evidence of periodontitis was found in 48.5% of the subjects, with carotid calcification in 18.6%. The intraclass correlation score for PMX findings of carotid calcification and stroke was 0.24 (95% CI: 0.10-0.35, P < 0.001). The odds ratio for PMX carotid calcification and periodontitis was 2.1 (95% CI: 1.3-3.2, P < 0.001), and for PMX carotid calcification and stroke 4.2 (95% CI: 1.9-9.1, P < 0.001). The associations disappeared when smoking was accounted for. A history of a heart attack was associated with stroke, gender, age, and PMX scores of alveolar bone loss. CONCLUSIONS: PMXs may provide valuable information about both oral conditions and signs of carotid calcification, data that are consistent with self-reported health conditions. Alveolar bone loss as assessed from PMXs is associated with cardiovascular diseases.

Localization of Knops system antigens in the long homologous repeats of complement receptor 1.

BACKGROUND: The Sl(a) (Knops system) located on complement receptor 1 (CR1) has been associated with malarial rosetting, a process associated with severe malarial infections. Moreover, the long homologous repeats (LHRs) B and C of CR1 were implicated in rosette formation. As a step toward mapping the location of Knops system antigens, truncated CR1 proteins have been expressed and their ability to inhibit antibodies to the high-incidence Knops system antigens was assessed. STUDY DESIGN AND METHODS: Individual LHRs (A, B, C, and D) of CR1 of the common CR1*1 (F) allotype were expressed as secreted forms in 293T cells. Their abilities to specifically neutralize Knops system antibodies were tested by both hemagglutination and flow cytometry. RESULTS: Three examples of anti-Kn(a) (n = 6) were almost completely inhibited by LHR-C and three by LHR-D. Two examples of anti-McC(a) (n = 2) and seven examples of anti-Sl(a) (n = 8) were inhibited by LHR-D. Both examples of anti-Yk(a) (n = 2) were partially inhibited by LHR-D. CONCLUSION: The high-incidence Knops system antigens reside within LHR-D and to a lesser extent within LHR-C. Because of the role of Sl(a) antigen in malaria rosetting, these results indicate that LHR-D may represent an additional malaria interaction region in CR1.

A homologous naturally occurring mutation in Duffy and CCR5 leading to reduced receptor expression.

Genetic variations in the CC chemokine receptor (CCR5) leading to reduced or absent expression are associated with resistance to human immunodeficiency virus infection and delayed onset of acquired immunodeficiency syndrome. Similarly, lack of the red-cell chemokine receptor Duffy confers protection against malarial infection by Plasmodium vivax. Investigators have previously described a missense mutation (R89C) in the first intracellular loop of Duffy that results in reduced protein expression. The present study shows that the lower Duffy expression is due to loss of the positive charge at this position, resulting in protein instability. Moreover, R60S, a mutation in the first intracellular loop of CCR5 noted in a recent cohort study, likewise results in reduced surface expression and function of CCR5. The presence of a homologous, naturally occurring mutation that may be protective against disease thus defines a novel mechanism accounting for the decreased expression of these receptors in some individuals. (Blood. 2001;97:3651-3654)

Mid-thoracic tenderness: a comparison of pressure pain threshold between spinal regions, in asymptomatic subjects.

Palpation for tenderness forms an important part of the manual therapy assessment for musculoskeletal dysfunction. In conjunction with other testing procedures it assists in establishing the clinical diagnosis. Tenderness in the thoracic spine has been reported in the literature as a clinical feature in musculoskeletal conditions where pain and dysfunction are located primarily in the upper quadrant. This study aimed to establish whether pressure pain thresholds (PPTs) of the mid-thoracic region of asymptomatic subjects were naturally lower than those of the cervical and lumbar areas. A within-subject study design was used to examine PPT at four spinal levels C6, T4, T6, and L4 in 50 asymptomatic volunteers. Results showed significant (P<0.001) regional differences. PPT values increased in a caudal direction. The cervical region had the lowest PPT scores, that is was the most tender. Values increased in the thoracic region and were highest in the lumbar region. This study contributes to the normative data on spinal PPT values and demonstrates that mid-thoracic tenderness relative to the cervical spine is not a normal finding in asymptomatic subjects.

First example of anti-Kx in a person with the McLeod phenotype and without chronic granulomatous disease.

BACKGROUND: Kx is lacking in the RBCs of patients with the McLeod syndrome. This condition is sometimes associated with chronic granulomatous disease (CGD). If given allogeneic RBCs, CGD patients with the McLeod phenotype may produce anti-Kx and anti-Km, and only phenotypically matched McLeod blood would be compatible. McLeod phenotype persons without CGD have made anti-Km but not anti-Kx (2 examples), and thus both McLeod and K(O) blood would be compatible. CASE REPORT: RBCs from a transfused patient with the McLeod phenotype but not with CGD (non-CGD McLeod) were typed for the Kell blood group antigens, and the plasma was analyzed for the presence of antibody by agglutination. The molecular basis was determined by analyzing for XK protein on RBC membranes by Western immunoblotting, by sequencing the XK gene, and by RFLP. RESULTS: The RBCs did not react with anti-Kx + anti-Km and showed weakening of Kell system antigens. The patient's plasma reacted moderately (2+) with RBCs of common Kell type and strongly (4+) with K(O) RBCs and RBCs of common Kell type treated with dithiothreitol, and did not react with McLeod RBCs. XK protein was absent from the RBC membranes. The XK gene had a point mutation in the donor splice site of intron 1 (G>C). CONCLUSION: This is the first report describing the molecular alteration in a non-CGD McLeod patient who has made anti-Kx. The immune response of people with the McLeod phenotype can vary, and K(O) blood may not always be compatible.

The use of cluster sampling to determine aid needs in Grozny, Chechnya in 1995.

War broke out in Chechnya in November 1994 following a three-year economic blockade. It caused widespread destruction in the capital Grozny. In April 1995 Medical Relief International--or Merlin, a British medical non-governmental organisation (NGO)--began a programme to provide medical supplies, support health centres, control communicable disease and promote preventive health-care in Grozny. In July 1995 the agency undertook a city-wide needs assessment using a modification of the cluster sampling technique developed by the Expanded Programme on Immunisation. This showed that most people had enough drinking-water, food and fuel but that provision of medical care was inadequate. The survey allowed Merlin to redirect resources earmarked for a clean water programme towards health education and improving primary health-care services. It also showed that rapid assessment by a statistically satisfactory method is both possible and useful in such a situation.

Identification of adult populations at high risk for dental caries using a computerized database and patient records: a pilot project.

OBJECTIVES: The purpose of this study is to test the usefulness of dental insurance claims history, supplemented with radiographic caries diagnoses, as a means of identifying caries-active and caries-inactive working adults, as determined by bacterial levels. Computerized identification of at-risk groups may facilitate subject selection for clinical trials designed to test caries-preventive strategies. METHODS: Two groups of subjects were initially selected from an insurance database based upon their dental service utilization during a one-year period: a "low restorative" group of individuals defined as persons who had received no restorative treatment, and a "high restorative" group comprised of individuals who had received at least three multisurfaced restorations. A chart review confirmed a diagnosis of caries in the high restorative group and an absence of caries in the low restorative group. Subjects were then approached for saliva collection. The low and high restorative groups were compared for salivary mutans streptococci and lactobacilli levels, stimulated flow rate, and buffer capacity (n = 48). RESULTS: The high and low restorative groups differed in mutans streptococci levels, but not on other measures. CONCLUSIONS: A group of subjects who had recently received multisurfaced restorations that were placed for reasons of caries had significantly higher levels of mutans streptococci and potential for continued caries activity when compared to a group of subjects who had received no restorations and were caries free.