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Biomedical subjects

J McIntyre

Publications and source records attributed to J McIntyre.

At least 37 records · Page 2Linked to original sources
PubMed2000

The Gardos channel is responsible for CDNB-induced dense sickle cell formation.

The red blood cells (RBCs) derived from blood taken from homozygous sickle cell (SS) patients demonstrate densities that are inversely proportional to the intracellular reduced glutathione (GSH) content. Addition of 1 mM 1-chloro-2,4-dinitrobenzene (CDNB) to low-density sickle cells (LDSS), at 4 degrees C, results in a shift of LDSS erythrocytes to high-density sickle cells (HDSS), with corresponding decreases in GSH. We have previously demonstrated that this CDNB effect was due to increased K(+) leakage and that dense cell formation could be inhibited by clotrimazole (specific for the Gardos channel) but not DIOA (specific for the K(+)-Cl(-) co-transport system) at pH 7.4 (Shartava et al. Am. J. Hematol. 1999;62:19-24). Here we demonstrate that clotrimazole (10 microM) inhibits dense cell formation at pH 7.1 and 6.8, while DIOA (1 mM) has no effect. As pH 6.8 is the optimal pH for the K(+)-Cl(-) co-transport system, we can now reasonably conclude that damage to the Gardos channel is responsible for CDNB-induced dense cell formation.

Anemia, Sickle Cell↗
PubMed2000

In vitro assessment of the structural integrity of the female condom after multiple wash, dry, and re-lubrication cycles.

Since the introduction of the female condom in the early 90s, there have been numerous reports of reuse of the device. In response to these reports, studies were undertaken to evaluate the safety of female condom reuse. If reuse were shown to be safe, then programmatic costs of introduction of the female condom would be reduced allowing it to be more widely available. This article outlines the results of in vitro structural integrity testing of the female condom after multiple wash, dry, and re-lubrication cycles. Devices were tested up to 10 washes using water leakage, burst, and tensile seam testing. All results were compared to the United States Food and Drug Administration (US FDA) standards for an unused female condom. The results of the structural integrity tests for all 6 washing procedures examined in this study were above the FDA minimum standards for seam strength and burst tests. For the water leakage test, 3 of 6 washing procedures tested passed the required FDA minimum standards (no holes detected). From the results of the study, it seems that washing, drying, and re-lubricating the female condom up to 10 times leads to some deterioration in the structural integrity of the device for specified washing procedures. Further studies are currently being conducted to establish the safety of female condom reuse with respect to microbial retention, structural integrity after in vivo use, and viral permeability.

Single-Use Internal Condom↗
PubMed2000

Unlicensed and off label prescribing of drugs in general practice.

AIM: To determine the incidence and nature of unlicensed and off label prescribing of drugs for children in general practice. METHODS: A retrospective analysis of all prescriptions for one year involving children (aged 12 years or under) from a single suburban general practice in the English Midlands. Prescribed drugs were categorised as licensed, unlicensed (without a product licence), or used in an off label way (outside the terms of their product licence). RESULTS: During 1997 there were 3347 prescription items involving 1175 children and 160 different drugs. A total of 2828 (84. 5%) prescriptions were for licensed medicines used in a licensed way; 10 (0.3%) were for unlicensed medicines; and 351 (10.5%) were licensed medicines used in an off label way. For 158 (4.7%) the information was insufficient to determine licence status. CONCLUSION: This is the first study to show that a significant number of drugs prescribed for children by general practitioners are off label and highlights the anomalies and inadequacies of drug information for prescribers.

Child↗
PubMed2000

Analysis of pointing errors reveals properties of data representations and coordinate transformations within the central nervous system.

The execution of a simple pointing task invokes a chain of processing that includes visual acquisition of the target, coordination of multimodal proprioceptive signals, and ultimately the generation of a motor command that will drive the finger to the desired target location. These processes in the sensorimotor chain can be described in terms of internal representations of the target or limb positions and coordinate transformations between different internal reference frames. In this article we first describe how different types of error analysis can be used to identify properties of the internal representations and coordinate transformations within the central nervous system. We then describe a series of experiments in which subjects pointed to remembered 3D visual targets under two lighting conditions (dim light and total darkness) and after two different memory delays (0.5 and 5.0 s) and report results in terms of variable error, constant error, and local distortion. Finally, we present a set of simulations to help explain the patterns of errors produced in this pointing task. These analyses and experiments provide insight into the structure of the underlying sensorimotor processes employed by the central nervous system.

Central Nervous System↗
PubMed1999

Gravity affects the preferred vertical and horizontal in visual perception of orientation.

The aim of this study was to evaluate the influence of gravity on the representation and storage of visual orientation information. On earth, measurements of response time and variability for a task of aligning remembered visual stimuli showed a distinct preference for horizontally and vertically oriented stimuli when the body and gravitational axes were aligned. This preference was markedly decreased or disappeared when the body axis was tilted with respect to gravity but was maintained for tests performed in microgravity. We conclude that subjects acquire and store visual orientation in a multi-modal reference frame that combines proprioceptive and gravitational information when both are available.

Adult↗
PubMed1999

Viewer-centered and body-centered frames of reference in direct visuomotor transformations.

It has been hypothesized that the end-point position of reaching may be specified in an egocentric frame of reference. In most previous studies, however, reaching was toward a memorized target, rather than an actual target. Thus, the role played by sensorimotor transformation could not be disassociated from the role played by storage in short-term memory. In the present study the direct process of sensorimotor transformation was investigated in reaching toward continuously visible targets that need not be stored in memory. A virtual reality system was used to present visual targets in different three-dimensional (3D) locations in two different tasks, one with visual feedback of the hand and arm position (Seen Hand) and the other without such feedback (Unseen Hand). In the Seen Hand task, the axes of maximum variability and of maximum contraction converge toward the mid-point between the eyes. In the Unseen Hand task only the maximum contraction correlates with the sight-line and the axes of maximum variability are not viewer-centered but rotate anti-clockwise around the body and the effector arm during the move from the right to the left workspace. The bulk of findings from these and previous experiments support the hypothesis of a two-stage process, with a gradual transformation from viewer-centered to body-centered and arm-centered coordinates. Retinal, extra-retinal and arm-related signals appear to be progressively combined in superior and inferior parietal areas, giving rise to egocentric representations of the end-point position of reaching.

Adult↗
PubMed1999

Respiratory depression in children receiving diazepam for acute seizures: a prospective study.

The aim of this study was to determine the incidence of respiratory depression following the use of diazepam in children presenting with seizures. All children presenting with seizures to a children's A & E department over a period of 9 months were studied prospectively. Respiratory depression was defined as a fall in respiratory rate or oxygen saturation, or apnoea resulting in ventilation or resuscitation with bag-and-mask oxygen. There were 130 patient episodes involving 97 children who received treatment for their seizures before admission and/or in the A & E department. Administration of diazepam resulted in 122 patient episodes. The route of administration was rectal in 91 episodes, intravenous in 12 episodes, and both rectal and intravenous in 19 episodes. Eleven children had respiratory depression in relation to diazepam administration. Eight of these children required ventilation. The overall incidence of respiratory depression following the use of diazepam was 9%. The incidence of respiratory depression following diazepam given intravenously or rectally is high. The use of diazepam as first-line therapy for children with acute seizures needs to be reviewed.

Acute Disease↗
PubMed1999

Unlicensed and off label drug use in neonates.

AIM: To determine the extent of use of drugs that are either not licensed (unlicensed), or are outside the terms of their product licence (off label) in a neonatal intensive care unit. METHODS: A prospective study was conducted over 13 weeks. RESULTS: 455 prescription episodes were administered to 70 babies. 63 (90%) patients were given a drug that was either unlicensed or used in an off label way. 54.7% prescription episodes were off label, many for more than one reason, and 9.9% (45) were unlicensed; 35.4% (161) prescription episodes were licensed. CONCLUSION: The use of unlicensed and off label drugs in neonatal intensive care seems to be far greater than other paediatric settings. This highlights the difficulties faced by those trying to ensure safe and effective prescribing for neonates. Urgent action is required to resolve this situation.

Drug Approval↗
PubMed1999

The practice and prevalence of dry sex among men and women in South Africa: a risk factor for sexually transmitted infections?

OBJECTIVES: To establish the prevalence of "dry sex" practice in a South African periurban population. To investigate the reasons for and factors influencing the practice of dry sex and to evaluate dry sex practice as a risk factor for sexually transmitted disease (STD). DESIGN: Cross sectional sample survey. METHODS: A random community sample of men and women aged between 16 and 35 in Gauteng Province, South Africa, were interviewed regarding the practice of dry sex using a structured interviewer administered questionnaire. RESULTS: Dry sex practices were reported by 60% of men and 46% of women. Among younger individuals dry sex practice is far more common among the less educated, but there was no significant difference between education groups in the older respondents. A higher proportion of men practising dry sex than not practising dry sex reported having a past history of STD infection (56% versus 41%) although this difference was only marginally significant (p = 0.05). There was no difference in reported history of STD between women who practised dry sex and those who did not. CONCLUSIONS: This study shows that dry sex practice is common in this community. The younger less educated group were the most likely to practise dry sex. Dry sex practice was associated with an increased prevalence of self reported STDs in men but not in women.

Adolescent↗
PubMed1999

A staff dialogue on a socially distanced patient: psychosocial issues faced by patients, their families, and caregivers.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The following case of an HIV-positive woman who was diagnosed with cervical cancer during a twin pregnancy was discussed at the May, 1999 Schwartz Center Rounds. The patient was in drug rehabilitation having been dependent on crack cocaine, with a past history of syphilis and gonorrhea. She was single and her other children were in foster care. Initially she was suspicious and non-compliant. A plan was negotiated to biopsy the cervical lesion after cesarean section and with confirmation of malignancy she underwent radical surgery and subsequently radiotherapy. Despite the almost insurmountable social and educational distance between her and her caregivers, they managed to bond and facilitate care. Although there were compromises with which staff were uncomfortable, the relationship was maintained and continues.

Adult↗
PubMed1998

Short-term memory for reaching to visual targets: psychophysical evidence for body-centered reference frames.

Pointing to a remembered visual target involves the transformation of visual information into an appropriate motor output, with a passage through short-term memory storage. In an attempt to identify the reference frames used to represent the target position during the memory period, we measured errors in pointing to remembered three-dimensional (3D) targets. Subjects pointed after a fixed delay to remembered targets distributed within a 22 mm radius volume. Conditions varied in terms of lighting (dim light or total darkness), delay duration (0.5, 5.0, and 8.0 sec), effector hand (left or right), and workspace location. Pointing errors were quantified by 3D constant and variable errors and by a novel measure of local distortion in the mapping from target to endpoint positions. The orientation of variable errors differed significantly between light and dark conditions. Increasing the memory delay in darkness evoked a reorientation of variable errors, whereas in the light, the viewer-centered variability changed only in magnitude. Local distortion measurements revealed an anisotropic contraction of endpoint positions toward an "average" response along an axis that points between the eyes and the effector arm. This local contraction was present in both lighting conditions. The magnitude of the contraction remained constant for the two memory delays in the light but increased significantly for the longer delays in darkness. These data argue for the separate storage of distance and direction information within short-term memory, in a reference frame tied to the eyes and the effector arm.

Anisotropy↗
PubMed1998

The efficacy of reducing agents or antioxidants in blocking the formation of dense cells and irreversibly sickled cells in vitro.

We show that N-acetylcysteine (NAC) has the ability to cause statistically significant diminishment in the in vitro formation of irreversibly sickled cells (ISCs) at concentrations greater than 250 micromol/L. Other antioxidants, approved for human use (cysteamine, succimer, dimercaprol), were not efficacious. NAC had the ability to cause statistically significant conversion of ISCs formed in vivo back to the biconcave shape. NAC was also shown to reduce the formation of dense cells and increase the available thiols in beta-actin. We showed that diminishing reduced glutathione (GSH), by treatment with 1-chloro-2,4-dinitrobenzene, resulted in increased dense cells. We conclude the NAC blocks dense cell formation and ISC formation by targeting channels involved in cellular dehydration and beta-actin, respectively. The efficacy of NAC is probably due to its combined antioxidant activity and ability to increase intracellular GSH.

Acetylcysteine↗
PubMed1998

Hand trajectory formation during whole body reaching movements in man.

End-effector trajectory formation was studied during a reaching movement using the whole body. The movements of various parts of the body were measured with the optoelectronic ELITE system. Wrist reaching movement paths showed noticeable curvatures. The analysis of various marker onset latencies revealed that the wrist was the last to move, always after the head, knee or trunk, suggesting a subordinate role of the focal component with respect to the primary role of the equilibrium component. These results suggest that reaching wrist movements are subjected to whole-body equilibrium constraints in addition to constraints placed upon end-effector kinematics or the dynamic optimization of upper-limb movements.

Adult↗
PubMed1998

Hand trajectories of vertical arm movements in one-G and zero-G environments. Evidence for a central representation of gravitational force.

The purpose of the present experiment was to study the way in which the central nervous system (CNS), represents gravitational force during vertical arm pointing movements. Movements in upward (against gravity) and downward (with gravity) directions, with two different mass loads (hand empty and with a hand-held 0.5-kg weight) were executed by eight subjects in a normal gravitational environment. Movements by two cosmonauts, in the two directions, were also tested in a state of weightlessness. Analyses focused upon finger trajectories in the sagittal plane. Subjects in a normal gravitational environment showed curved paths for both directions and weight conditions. In addition, downward movements showed significantly smaller curvatures than upward movements. Movement times were approximately the same for all the experimental conditions. Curvature differences between upward and downward movements persisted during space flight and immediately postflight. Movement times from both cosmonauts increased slightly during flight, but returned to normal immediately on reentry in a one-G environment. Results from the present study provide evidence that gravity is centrally represented in an anticipatory fashion as a driving force during vertical arm movement planning.

Adult↗
PubMed1998

Child extrafamilial sexual abuse: predicting parent and child functioning.

OBJECTIVE: This study evaluated the emotional and behavioral adjustment of parents and children within 3 months and 1 year after the discovery of child extrafamilial sexual abuse. METHOD: Ninety-two case parents (63 mothers, 29 fathers) and 56 children were compared to a nonclinical comparison group of 136 parents (74 mothers, 62 fathers) and 75 children. Parent adjustment was assessed using self-report measures while child functioning was assessed using a combination of child-, parent- and teacher-report measures. RESULTS: Mothers, fathers and sexually abused children experienced clinically significant effects both initially and at 12 months post-disclosure. Children's perceptions of self-blame and guilt for the abuse and the extent of traumatization predicted their self-reported symtomatology at 3 months and 1 year post-disclosure. Child age and gender also significantly contributed to the prediction of many of the child outcome measures. No abuse-related variable was related to any child self-report measure. Mothers' satisfaction in the parenting role, perceived support and intrusive symptoms predicted their initial emotional functioning. Avoidant symptoms, child's internalizing behavior and mothers' initial emotional functioning were significant predictors of longer-term emotional functioning. CONCLUSIONS: Results emphasize the need to address children's abuse-related attributions and underscore the need to expand our focus beyond the child victims to the traumatized families.

Adolescent↗
PubMed1998

Reference frames and internal models for visuo-manual coordination: what can we learn from microgravity experiments?

Gravity plays a role in many different levels of human motor behavior. It dictates the laws of motion of our body and limbs, as well as of the objects in the external world with which we wish to interact. The dynamic interaction of our body with the world is molded within gravity's constraints. The task of catching a ball that has been thrown toward a human subject typifies the kind of constraints that the nervous system must take into consideration during visuo-manual coordination on earth. By dissecting and examining the components of this task, one can see what kinds of problems must be solved by the central nervous system to generate coordinated motor actions in response to incoming sensory information. In this review, we use the example of a ball catching task to outline various issues in the field of human motor control and to ask the question as to how the microgravity environment of lower earth orbit can be used to probe the functioning of the human motor system.

Hand↗