Post-injection sciatic neuropathy in a cynomolgus macaque (Macaca fascicularis).

BACKGROUND: Intramuscular injection is a common route parenteral used in primates. METHODS: A cynomolgus macaque was evaluated for acute lameness and atrophy of the left leg with no evidence of trauma. RESULTS: History revealed ketamine injection 12 days prior. CONCLUSIONS: Histologic examination supported traumatic injection neuropathy due to intramuscular injection.

Real-time telemetric monitoring in whole-body 60Co gamma-photon irradiated rhesus macaques (Macaca mulatta).

BACKGROUND: Animals undergoing experimental manipulations, such as exposure to radiation, may exhibit physiologic and behavioral signs of pain and distress. Telemetry permits close monitoring of these parameters for early and effective management during procedures. METHODS: Radiotelemetric units were surgically implanted into 24 Macaca mulatta before 6.5-Gy cobalt-60 γ-photon irradiation. Each unit transmitted electrocardiogram, intrathoracic pressure, and body temperature leads. Primate irradiation-restraint boxes and housing cages were modified to collect telemetric signals before, during, and after irradiation. RESULTS: Differences in respiratory rate, heart rate, or body temperature in telemetric-collected recordings, which were observed during non-irradiation and irradiation sessions, were statistically insignificant. CONCLUSIONS: Insignificant changes in the physiological parameters during monitoring suggest that the animals experienced no detectable pain or distress during irradiation.

Resident bacteria in a mixed population of rhesus macaque (Macaca mulatta) monkeys: a prevalence study.

BACKGROUND: Microflora populations residing in oropharyngeal and gastrointestinal sites defend against pathogenic bacterial colonization. Perturbations in these microbial communities may allow opportunistic pathogenic bacteria to establish themselves and cause morbidity and mortality from sepsis particularly after stressful experimental procedures. This study determined the prevalent facultative bacteria in a resident population of Macaca mulatta prior to use in experimentally induced immunosuppressive radiation studies. METHODS: Standard microbiological methods were used to assess prevalent facultative bacteria in the oropharynx and rectum of 24 male M. mulatta. RESULTS: The majority of the bacteria isolated from the oropharyngeal and rectal sites were gram-positive cocci. Species of Staphylococcus and Streptococcus predominated in all samples. Few gram-negative bacteria were isolated. CONCLUSIONS: Bacteriological assessment is recommended to identify predominant bacterial species to be prepared to provide appropriate antimicrobial therapy in non-human primates that are expected to undergo stressful immunocompromising procedures.

[Omalizumab and allergen immunotherapy: A clinical report and review of the literature]. / Omalizumab et immunothérapie allergénique : cas clinique et revue de la littérature.

INTRODUCTION: Several authors have proposed combined omalizumab and allergen immunotherapy (AIT) in patients suffering from severe allergic asthma to both increase disease control and decrease the severity through targeting the main allergen responsible for the respiratory symptoms. OBSERVATION: In a female pediatric patient suffering from severe asthma, followed-up at the University Hospital of Montpellier (France), we prescribed an AIT to Alternaria after obtaining symptom control with omalizumab. The patient showed an overall improvement in symptoms after AIT was administered and the disease remained controlled long after cessation of omalizumab. CONCLUSIONS: There are only a few publications evaluating the efficacy of the association of these two biotherapies in the management of severe allergic asthma. In addition there is, as yet, no common protocol for the administration of the two prescriptions. This approach to treatment would benefit from standardization in order to optimize the management of severe allergic asthma.

The Case for Computational Health Science.

In this introductory paper, we begin by making the case for Computational Health Science, which we define as the interdisciplinary efforts of health scientists, computer scientists, engineers, psychologists, and other social scientists, to conduct innovative research that will inform future practice directed at changing health behavior through improved communication, networking, and social capital. We recognize and discuss some of the main challenges involved with such an enterprise, but also highlight the associated benefits, which, we argue, significantly outweigh them. We then provide a brief summary of the contributions to this first Special Issue on Computational Health Science.

RFrAP: a computer program for analysis of complex HLA RFLPs. Assignment of restriction fragments to haplotypes by segregation analysis.

The availability of HLA class II cDNA probes has led to the development of a powerful method for the discrimination of genetic variation in this region of the major histocompatibility complex. There are problems with this approach which reduce its usefulness, including the hybridization of a probe with multiple restriction fragments (RFs) from the same locus or of two different cDNA probes with the same RF (cross-hybridizing). These problems may now be largely overcome by the relatively simple computer program presented here, which allows the entry, storage, and editing of phenotype data. It includes utilities for the automatic assignment of bands to haplotypes and also statistical functions to determine several types of correlations. The outputs are presented in a format familiar to HLA serologists and immunogeneticists. In addition, the data is stored in a manner that allows the user to easily prepare "ad hoc" figures and tables that illustrate the more complex relationships among bands and between them and other variables.

DQA1 restriction fragment length polymorphisms and insulin-dependent diabetes mellitus: a BglII fragment labels a subset of B8,DR3 haplotypes uniquely associated with insulin-dependent diabetes mellitus.

Class II restriction fragment length polymorphism studies of 38 pedigrees with multiple cases of insulin-dependent diabetes mellitus revealed the existence of a DQA1-related polymorphism that distinguishes two kinds of HLA-B8,DR3 haplotypes. One of these, characterized by the presence of DQA1-BglII 7.20 kb, was present in all 14 examples inherited by patients and in 6 of the 12 B8,DR3 haplotypes not so inherited. The apparently complete association between the presence of this fragment and the "affected" status of B8,DR3 haplotypes (p = 0.004) was confirmed in a separate group of 26 simplex pedigrees selected for the presence of this haplotype in the respective probands (combined p less than 0.0001).

Definition of IDDM-associated HLA DQ and DX RFLPs by segregation analysis of multiplex sibships.

Genetic variation of the DQ alpha and beta and of the DX alpha genes, detectable as RFLP in genomic DNA digests, has been suggested to improve the identification of individuals at high risk for insulin-dependent diabetes mellitus (IDDM). DNA from all members of 32 IDDM multiplex families was digested with six restriction endonucleases and the resulting fragments analyzed in Southern blots for hybridization with labeled cDNA probes for those genes. A computerized segregation analysis procedure was then used to assign fragments to haplotypes. Associations among fragments and between fragments and haplotypes characterized serologically and biochemically for their class II genes and IDDM-carrier status were calculated. The results indicate that the alleles of the DX alpha polymorphism maintain linkage disequilibrium with those of the DQ beta genes responsible for the well-known DQ beta 3.2-IDDM association, so that IDDM-carrier haplotypes carry disproportionally often both DQ beta 3.2 and DX alpha-TaqI-2.2kb. Thus, these RFLPs identify a DR-DQ-DX haplotype in high linkage disequilibrium, rather than the locus or loci that account for their high relative risk. However, four DR4-DQ beta 3.2 haplotypes that lack DX alpha-TaqI-2.2kb were encountered, two of which are "affected." These haplotypes suggest that the identification of the "disease locus" can be facilitated by the study of unusual haplotypes in which distinct IDDM-associated alleles occur separated from their neighbors of the standard genetic configurations.

Molecular characterization by high-resolution isoelectric focusing of the products encoded by the class II region loci of the major histocompatibility complex in humans. I. DR and DQ gene variants.

We describe a new approach to the analysis of the structural polymorphism of the DR beta, DQ alpha, and DQ beta polypeptide chains of human histocompatibility class II antigens. In comparison to conventional two-dimensional gel studies, this method provides sharper definition of the protein bands and side-by-side comparisons within the same gel, thereby permitting the detection of minor differences in the isoelectric points of the protein chains. Using this methodology we have analyzed the IEF polymorphism and the variability in the number of the DR beta chains encoded by different DR haplotypes. Twenty DR beta chain variants, which include the products of no less than two separate DR beta loci, have been thus far identified. Alleles at one of these loci are assumed to code for DR beta chains carrying the DR alloespecificities DR1, DR2, DR3, DR4, DR5, DRw6, DR7, and DR8. Alleles at a second DR beta locus encode DR beta chains that may be shared by serologically DR-different haplotypes and carry supertypic serologic specificities (i.e., DRw52 and DRw53). We also demonstrate here that the structural polymorphisms of the DQ alpha and DQ beta chains are more extensive than previously thought, report the characterization of 14 DQ beta variants, and define their relationship to the previously described DQw serologic specificities. In addition, we describe the class II haplotype associations observed for the different DR and DQ variants characterized.

HLA antigens and islet cell antibodies in gestational diabetes.

The HLA antigens of 136 patients with gestational diabetes are compared with control populations. No significant variations are observed in their frequencies, particularly for those antigens associated with Type 1 diabetes mellitus. Islet cell antibodies have also been studied in the serum of 52 of these patients and 20 of them were positive, whereas only one of 37 pregnant nondiabetic women had such antibodies (chi 2 = 15.2). A very high association between ICA and DR3 and DR4 was encountered (chi 2 = 17, with two df); half of the patients positive for either one of these antigens were ICA positive. These results indicate that ICA associates equally with DR3 and DR4, against the hypothesis that this expression of autoimmunity is more a characteristic of DR3- than of DR4-associated genetic susceptibility. These patients will be followed to determine if the ICA+ individuals are at increased risk for the development of insulin-dependent diabetes.

Measurements from normal umbilical cord blood of four lysosomal enzymatic activities: alpha-L-iduronidase (Hurler), galactocerebrosidase (globoid cell leukodystrophy), arylsulfatase A (metachromatic leukodystrophy), arylsulfatase B (Maroteaux-Lamy).

Umbilical cord blood (UCB) has received increasing attention as a source of unrelated hematopoietic stem cells for transplantation. Lysosomal diseases have been effectively treated and normal enzymatic activity has occurred subsequent to engraftment using UCB. The use of donor cells with normal amounts of enzyme, rather than those from carriers whose level may be 50% or less, is an obvious goal. The frequency of such heterozygotes varies from 1:10 to 1:140 or lower depending upon the disease at issue. We assayed the levels of lysosomal enzymes in normal UCB in random samples as well as those used for transplantation. We measured the following enzymatic activities: alpha-l-iduronidase (Hurler), galactocerebrosidase (globoid cell leuko- dystrophy) and arylsulfatase A (metachromatic leukodystrophy). For the latter, levels of activity in UCB are comparable to those found in adult blood. In the case of arylsulfatase B (Maroteaux-Lamy) a level lower than adult level was found. An informed choice by the transplanting physician based on the activity of the relevant enzyme in the UCB donor will provide a better opportunity for an improved prognosis for more complete correction of the recipient's primary disease. Bone Marrow Transplantation (2000) 25, 541-544.

Double-blind trial of amineptine and clomipramine in the treatment of depression.

A double-blind trial was carried out in 62 depressed patients to compare the clinical efficacy and acceptability of amineptine and clomipramine. Patients were allocated at random to one or other of two treatment groups and received daily doses of amineptine ranging from 100 to 300 mg (mean 180 mg) or of clomipramine ranging from 50 to 150 mg (mean 84 mg) over a period of 6 weeks. Global assessment of response to treatment and Hamilton Rating Scale scores, assessed before and after 1,3 and 6 weeks of treatment, indicated that the two drugs appeared to be equally effective and no differences between them could be demonstrated in the analysis of the individual items or grouped items of the scale used. Measurements of ocular tone showed that there was significantly less risk of amineptine producing an increase in tone, and blood pressure and electrocardiographic investigations also underlined the greater cardiovascular tolerance of amineptine. Five (16%) of the 32 patients in the clomipramine group were withdrawn from the study because of adverse effects.

Fast point spread function computation from aperture functions in high-resolution positron emission tomography.

The problem of extracting point spread functions from detector aperture functions in high-resolution PET is addressed. In the limit of very small size detectors relative to the ring dimensions, assumptions are made that lead to a fast and simple computation model yielding point spread functions with negligible errors due to the reconstruction algorithm. The methods allows one to assess accurately the intrinsic performance of a PET tomograph, and it appears to be adequate to relate the imaging capabilities in every point of the camera reconstruction field to the geometric and physical characteristics of the detection system. The method was developed as an investigation tool to help design the next generation of very-high-resolution PET tomographs.

A stationary sampling scheme for multilayer positron tomographs.

A stationary sampling scheme applicable to tomographic instruments incorporating two or more detector layers is described and tested. In this concept, the detectors in adjacent layers are angularly offset by half the interdetector distance. By reconstructing in one single slice all lines of response defined by two adjacent rings of detectors, a fourfold increase in the number of coincidence lines is obtained and a uniform sampling distance equal to one-quarter the interdetector spacing is achieved. Whereas this is obtained at the expense of a 100% degradation of the resolution in the axial direction, with the recent breed of PET (positron emission tomography) scanners using nearly square cross section detectors, the resolution loss may be tolerable in many situations. In addition, normal reconstruction of the individual coincidence planes is always possible. The sampling concept was investigated experimentally with the help of the Universite de Sherbrooke PET camera simulator.

Quantitative analysis of T and B cell subsets in healthy and sick premature infants.

This work proposes a serial quantitative analysis of the numbers and percentages of B and T cell subsets in 104 consecutive premature infants (PI) between birth and six months of age as compared with 21 normal term infants. First, in order to ascertain the effects of perinatal distress at birth (respiratory distress, neonatal asphyxia) on certain parameters of the immune system, the PI were divided into two groups. One comprised 36 healthy preterms, the other, 68 preterms with perinatal distress. It was then shown that healthy PI differed from full-term infants by their higher absolute numbers of T cells (CD2-positive) and helper T cell subset (CD4-positive). These increases in CD2- and CD4-positive cells correlated with gestational age (GA). An increase in B lymphocytes (CD20-positive cells) was also documented but no correlation with GA could be seen. Secondly, perinatal distress was found to be concomitant with transient decrease in percentages and absolute numbers of CD2- and CD4-positive cells, particularly in PI of less than 28 weeks of gestation. The B cells (CD20- and CD21-positive cells) were not different in absolute numbers. Respiratory distress had a more discernable effect than fetal asphyxia on the immune system. Finally, no immunological parameters tested could at any time predict the occurrence of infection in PI during the first 6 months of life.

Relationship of learning styles to preferences for instructional activities.

One hundred and sixty-three dental hygiene students and 26 dental hygiene faculty participated in a study to examine the relationship between learning styles and preference for 13 instructional activities. The results indicated that most students and faculty were located in Kolb's "accommodator" and "diverger" learning style categories. These two learning style groups differed in their preferences for group-oriented activities. Faculty were able to predict their students' predominant learning styles.

Tolerance of the Passy-Muir Speaking Valve in infants and children less than 2 years of age.

Research literature confirms the intuitive reasoning that tracheotomy may adversely influence speech acquisition in infants and children. The Passy-Muir Speaking Valve (PMSV) permits inspiration through the tracheotomy stoma and expiration through the glottis, allowing for phonation. Although adults with tracheostomies have demonstrated the ability to speak using the valve without respiratory compromise, there is scant literature regarding the use of this valve in the infant or child population. A retrospective review of 64 charts was conducted to examine documented evidence of tolerance of the PMSV in infants and children 2 years of age and less. Of the 29 children trialed, 24 (83%) tolerated the PMSV and 75% of those children produced vocalization on the first trial. Another 21% produced vocalization on a subsequent trial. The implications of this study indicate that the speaking valve is safe for use in infants as young as 13 days of age when the child is trialed in a monitored setting using appropriate guidelines.

Use of self-generated and supplied visuals as mnemonics in gifted children's learning.

In accordance with ancient belief and recent research, we hypothesized that self-generated imagery techniques of gifted children would be superior to supplied (experimenter-provided) visuals in facilitating recall and recognition on a memory task. 27 high-potential students in Grades 4 to 6 were divided into three treatment groups to investigate the effects of rote repetition, self-generated visualization, and supplied visuals on the memorization of concrete noun-word pairs. Perhaps because even gifted children do not know how to construct good visual images without training and practice, our hypothesis was not supported. The supplied visual condition produced significantly better results than did either of the other treatment conditions, implying that the utilization of appropriate techniques helps gifted children learn certain memory tasks. However, one wonders if effective instruction in the development of self-generated mnemonic techniques might not be of greater benefit to young learners of such tasks.

Anterior transarticular screw fixation for atlantoaxial arthrodesis: A report of two cases.

The sequelae of atlantoaxial instability (AAI) range from axial neck pain to life-threatening neurologic injury. Instrumentation and fusion of the C1-2 joint is often indicated in the setting of clinical or biomechanical instability. This is the first clinical report of anterior Smith-Robinson C1-2 transarticular screw (TAS) fixation for AAI. The first patient presented with ischemic brain tissue secondary to post-traumatic C1-2 segment instability from a MVC 7 years prior to presentation. The second patient presented with a 3 year history of persistent right-sided neck and upper scalp pain. Both were treated with transarticular C1-2 fusion through decortication of the atlantoaxial facet joints and TAS fixation via the anterior Smith-Robinson approach. At 16 months follow-up, the first patient maintained painless range of motion of the cervical spine and denied sensorimotor deficits. The second patient reported 90% improvement in her pre-operative symptoms of neck pain and paresthesia. Anterior Smith-Robinson C1-2 TAS fixation provides a useful alternative to the posterior Goel and Magerl techniques for C1-2 stabilization and fusion.

Left ventricular pressure measurement by telemetry is an effective means to evaluate transplanted heart function in experimental heterotopic cardiac xenotransplantation.

Evaluation of the function of heterotopic cardiac transplants has traditionally been accomplished by either manual palpation or serial biopsies. Both methods have drawbacks. Palpation can be difficult to differentiate a pulse from the graft versus a transmitted pulse from the native aorta. Serial biopsies, though accurate, require multiple laparotomies, leading to increased morbidity and possibly mortality rates. In this study we used an advanced telemetry system, consisting of an intra-abdominal implant, that was capable of continuously monitoring simultaneously several parameters of the transplanted heart and the status of the recipient. In a large animal model of heterotopic cardiac xenotransplantation (pig donor to baboon recipient), we implanted the device in 12 animals: 8 with and 4 without immunosuppression. We monitored and continuously recorded the left ventricular pressure (both peak-systolic and end-diastolic [LVEDP]), heart rate, and the electrocardiogram pattern of the transplanted heart as well as the temperature of the recipient. The left ventricular pressure proved to be the most valuable parameter to assess graft heart function. In the 4 nonimmunosuppressed cases, grafts were rejected acutely. In these cases, the end-diastolic pressure increased sharply and the heart stopped contracting when the difference between the systolic and the diastolic pressure decreased to <10 mm Hg. The earliest reproducible sign of rejection was an increased LVEDP. Among long-term survivors, the increase in diastolic pressure was gradual, indicating progressive thickening of the myocardium and decreased compliance of the ventricle. Six of 8 immunosuppressed animals died of other complications before rejecting the transplanted heart. The telemetry was also helpful to indicate early onset of fever in the recipients, thus allowing us to intervene early and prevent potentially lethal septic complications. Continuous monitoring of several parameters via telemetry allowed detection of changes associated with rejection as well as other complications at an early stage, allowing prompt intervention, treatment, and possibly reversal of rejection.