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Biomedical subjects

M Turner

Publications and source records attributed to M Turner.

At least 91 records · Page 5Linked to original sources
PubMed1999

Dermatologic manifestations of Hermansky-Pudlak syndrome in patients with and without a 16-base pair duplication in the HPS1 gene.

BACKGROUND: Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency, and lysosomal accumulation of ceroid lipofuscin. Patients with HPS from northwest Puerto Rico are homozygous for a 16-base pair (bp) duplication in exon 15 of HPS1, a gene on chromosome 10q23 known to cause the disorder. OBJECTIVE: To determine the dermatologic findings of patients with HPS. DESIGN: Survey of inpatients with HPS by physical examination. SETTING: National Institutes of Health Clinical Center, Bethesda, Md (a tertiary referral hospital). PATIENTS: Sixty-five patients aged 3 to 54 years were diagnosed on the basis of the absence of platelet dense bodies in individuals with albinism and a bleeding diathesis. The presence of a 16-bp duplication in HPS1 was determined by polymerase chain reaction amplification; 40 patients were homozygous for the duplication and 25 lacked the duplication. All patients with the duplication were from northwest Puerto Rico; all patients without the duplication were non-Puerto Rican except 4 from central Puerto Rico. RESULTS: Both patients homozygous for the 16-bp duplication and patients without the duplication displayed skin color ranging from white to light brown. Patients with the duplication, as well as those lacking the duplication, had hair color ranging from white to brown and eye color ranging from blue to brown. New findings in both groups of patients with HPS were melanocytic nevi with dysplastic features, acanthosis nigricans-like lesions in the axilla and neck, and trichomegaly. Eighty percent of patients with the duplication exhibited features of solar damage, including multiple freckles, stellate lentigines, actinic keratoses, and, occasionally, basal cell or squamous cell carcinomas. Only 8% of patients lacking the 16-bp duplication displayed these findings. As a group, the patients with the duplication lived closer to the equator than those without the duplication. CONCLUSION: Patients with HPS exhibit wide variation in pigmentation and dermatologic findings.

Adolescent↗
PubMed1999

Defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.

Vav, a guanine nucleotide exchange factor for members of the Rho family of small GTPases, is activated through engagement of B and T lymphocyte antigen receptors. It is important for establishing the signaling threshold of the TCR, as mice lacking Vav display defective thymocyte selection. Here, conventional B cells are shown to develop normally in Vav-deficient mice but these mice have few B-1 B cells. The threshold for inducing B cell proliferation through BCR engagement in vitro is greater in Vav-deficient B cells. Nevertheless, in vivo the mutant mice have normal antibody responses to haptenated Ficoll. In contrast, Vav-/- mice show defective class switching to IgG and germinal center formation when immunized with haptenated protein. Interestingly, this defect is reversed in chimeras where normal T cells are present. Antigen-specific proliferation of T cells in the T zone was found to be similar in wild-type and Vav-/- mice but the induction of IL-4 mRNA and switch transcripts was specifically impaired. These results suggest that defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.

Animals↗
PubMed1999

The CD45 tyrosine phosphatase regulates CD3-induced signal transduction and T cell development in recombinase-deficient mice: restoration of pre-TCR function by active p56(lck).

The pre-TCR complex regulates the transition from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP) thymocytes during T cell development. In CD45(-/-) mice there is an accumulation of DN cells, suggesting a possible role for CD45 in pre-TCR signaling. We therefore crossed CD45(-/-) with Rag-1(-/-) mice to investigate the signaling functions of the CD3 complex in DN thymocytes. Remarkably, treatment of Rag-1(-/-)/CD45(-/-) mice with a CD3 mAb caused maturation to the DP stage at only 3% of the level measured in Rag-1(-/-) mice. Furthermore, ligation of the CD3 complex on Rag-1(-/-) /CD45(-/-) thymocytes in vitro induced less tyrosine phosphorylation in specific proteins when compared to Rag-1(-/-) thymocytes. CD45(-/-) mice were also crossed with pLGFA mice expressing a constitutively active form of the lck tyrosine kinase which restored the DN to DP transition to near normal levels. Our results are consistent with a model in which CD45-activated p56(lck) is critical for pre-TCR signal transduction.

Animals↗
PubMed1999

Greatly reduced efficiency of both positive and negative selection of thymocytes in CD45 tyrosine phosphatase-deficient mice.

The T cell repertoire is shaped by positive and negative selection of thymocytes. TCR-mediated signals that determine these selection processes are only partly understood. The CD45 tyrosine phosphatase has been shown to be important for signal transduction through the TCR, but there has been disagreement about whether CD45 is a positive or negative regulator of TCR signaling. Using CD45-deficient mice expressing transgenic TCR, we show that in the absence of CD45 there is a large increase in the thresholds of TCR stimulation required for both positive and negative selection. Our results conclusively demonstrate that in double-positive thymocytes CD45 is a positive regulator of the TCR signals that drive thymic selection events.

Animals↗
PubMed1999

Hemodialysis adequacy in Network 5: disparity between states and the role of center effects.

The purpose of this study was to determine whether an observed difference in hemodialysis adequacy between states in Network 5 was due to variations in patient characteristics and to what extent dialysis center effects played a role in the observed disparity between states. This was a retrospective observational study of 6,969 patients dialyzed at centers in Maryland and Virginia. There were 3,919 patients on hemodialysis at 89 facilities in Virginia and 3,050 subjects dialyzed at 65 centers in Maryland. The mean urea reduction ratio (URR) was higher in Virginia compared with Maryland (68.2 +/- 0.1% v 66.0 +/- 0.2%, P < 0.0001, respectively), and there continued to be a mean difference in URR of 1.8% between VA and MD (P < 0.0001) after adjusting for several covariates. The differences in URR between states varied depending on facility proprietary status, size as measured by number of stations, and relationship to hospital (free-standing or hospital-based). Furthermore, the center where a patient dialyzed, when treated as a fixed effect, accounted for 15% of the variance in URR. The mean difference of 1.8% in URR between states persisted in a mixed-effects model that included all covariates along with adjusting for dialysis centers as a random effect. The disparity in dialysis adequacy between states in Network 5 could not be accounted for by demographic characteristics, case mix factors, or a large center effect observed in the region. Therefore, we conclude that underlying national reports on dialysis adequacy are heterogeneous results related to differences across regions such as states within a given Network. This difference between states is not explained by the strong center effect found on adequacy in this population of hemodialysis patients.

Blood Urea Nitrogen↗
PubMed1999

Single-handed practices--their contribution to an undergraduate teaching network in the first year of the new curriculum.

OBJECTIVES: The new curriculum at King's College School of Medicine and Dentistry, which commenced in September 1996, requires all medical undergraduates to have a general practice placement throughout the 5 years of their medical education. DESIGN: This paper discusses recruitment, training and support of teaching practices for the new curriculum, reviews the distribution of single-handed general practices in the network and, via a selection of monitoring and evaluation procedures, discusses the implications of a policy which is inclusive of single-handed practices. The findings relate to the experience of the first semester of the first year of the new curriculum. It also examines the contributions that single-handed practices have made to the teaching network and the kind of support needed, if single-handed practices are to continue to contribute to the King's teaching network. SETTING: King's College School of Medicine and Dentistry. SUBJECTS: Medical undergraduates. RESULTS: The findings of this paper revealed that over a third of general practice provision is via single-handed practices in South-east London. Within the undergraduate teaching network, 10% of practices are single-handed. Students are welcomed and receive a learning experience comparable to those students in larger practices. Attendance at training events has proved difficult for some of these tutors, but the extra input from the department, in order to address this deficit, has not been onerous. Indeed, single-handed practices have not been unique with regard to difficulties in attendance at training events. CONCLUSIONS: The study concludes that single-handed practices can make satisfactory provision for undergraduates in the new curriculum and there is no evidence from this study to suggest otherwise.

Curriculum↗
PubMed1999

Motion sickness in public road transport: the effect of driver, route and vehicle.

Relationships between vehicle motion and passenger sickness have been investigated in a survey of 3256 passengers travelling on 56 mainland UK bus or coach journeys. Vehicle motion was measured throughout all journeys, yielding over 110 h of six-axis coach motion data from five types of coach and 17 different drivers. Overall, 28.4% of passengers reported feelings of illness, 12.8% reported nausea and 1.7% reported vomiting during coach travel. Passenger nausea and illness ratings increased with increased exposure to lateral coach motion at low frequencies (< 0.5 Hz). Motion in other axes correlated less well with sickness, although there were some intercorrelations between the motions in the different axes. Sickness levels among passengers were greater with drivers who drove to produce higher average magnitudes of fore-and-aft and lateral vehicle motion. Nausea occurrence was greater on routes classified as being predominantly cross-country where magnitudes of lateral vehicle motion were significantly higher. Lateral motion and motion sickness increased from the front to the rear of each vehicle. No significant differences in sickness were found between the five different vehicle types used in the study. The applicability of a motion sickness dose model to these data is discussed.

Humans↗
PubMed1999

Motion sickness in public road transport: passenger behavior and susceptibility.

The aim of this research was to identify personal and environmental factors influencing individual susceptibility to motion sickness during road transport. A questionnaire survey of 3256 coach travellers was conducted. Information on passenger characteristics, travel regularity, activity during travel, use of anti-motion sickness drugs and self-reported motion sickness susceptibility were collected over 56 private hire coach journeys. Details of the travel environment (visibility, temperature and seating) were also recorded. The relationship of these variables with passenger illness and more specific symptoms of motion sickness are examined. Overall, 28.4% of passengers reported feeling ill, 12.8% reported nausea and 1.7% reported vomiting during coach travel. Travel sickness decreased with increasing passenger age and greater travel experience. Females were more likely to report feeling ill during coach travel than males by a ratio of four to three. Poor forward visibility was found to increase sickness. Passenger illness occurrence was approximately three times higher for passengers with no view of the road ahead (mean, 34.6%) compared to passengers who could see the road ahead extremely well (mean, 12.7%). No relationships were found between the occurrence of travel sickness and temperature or time of travel. Differences in the pattern of sickness responses exhibited by coach travellers suggest: (1) habituation through greater travel regularity may occur independently of reductions in travel sickness that occur with age; (2) females are more affected by poor forward visibility than males; and (3) the incidence of travel sickness could be significantly reduced by improving the external visibility afforded to passengers.

Adolescent↗
PubMed1999

Malingering, hysteria, and the factitious disorders.

The arguments contained within this paper take as their starting point the suggestion that malingering is related along three separate continua to the nosological entities of antisocial behaviour, hysteria and the factitious disorders. The paper is both an attempt to show how these continua can be underwritten and at the same time a discussion of the aetiology of the disorders in question. It will be argued that the aetiological accounts of hysteria and the factitious disorders found in the psychiatric literature fail to make room for an account of the nature of the relationships of these disorders with malingering and thereby fail to fulfil the most important constraint on the acceptability of explanations in this area. In discussing the factitious disorders in the light of this constraint it will be suggested that psychodynamic explanations are vacuous and folk-psychological explanations in principle unavailable. With regard to hysteria it will be suggested that an explanatory account which embraces all the required phenomena and accommodates the close relationship of the disorder to malingering must make use of cognitive-psychologically informed account of self-deception which treats hysterical beliefs as beliefs which are formed as a result of a failure to accurately appraise the subjectively available evidence.

Journal Article↗
PubMed1999

Vasa previa: an avoidable obstetric tragedy.

UNLABELLED: Vasa previa is a rarely reported condition in which the fetal blood vessels, unsupported by either the umbilical cord or placental tissue, traverse the fetal membranes of the lower segment of the uterus below the presenting part. The condition has a high fetal mortality due to fetal exsanguination resulting from fetal vessels tearing when the membranes rupture. Despite improvements in medical technology, vasa previa often remains unsuspected until this fatal fetal vessel rupture occurs. Significant reduction in the fetal mortality from this condition depends on a high index of suspicion leading to antenatal diagnosis, and elective delivery by cesarean. We believe transvaginal ultrasound in combination with color Doppler is the most effective tool in the antenatal diagnosis of vasa previa and should be utilized in patients at risk, specifically those with bilobed, succenturiate-lobed, and low-lying placentas, pregnancies resulting from in vitro fertilization, and multiple pregnancy. Where there has been antepartum or intrapartum hemorrhage, especially when associated with fetal heart irregularities, we also recommend a test to exclude fetal blood in the vaginal blood. Similarly, amnioscopy before amniotomy may help to diagnose this condition. Cesarean delivery is the method of delivery of choice, and aggressive resuscitation of the affected neonate may be life saving. With a high index of suspicion, antenatal diagnosis using transvaginal sonography in combination with color Doppler, elective delivery by cesarean, and aggressive resuscitation of the neonate where fetal vessel rupture has occurred, the mortality from this complication may be considerably reduced. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to identify the risk factors and associated conditions for vasa previa, to identify the various clinical presentations and management of vasa previa, and to be aware of the diagnostic tools available to make the antepartum diagnosis of vasa previa.

Cesarean Section↗
PubMed1999

Carbon monoxide poisoning treated with hyperbaric oxygen: metabolic acidosis as a predictor of treatment requirements.

A retrospective case note analysis was made of patients who received hyperbaric oxygen for carbon monoxide poisoning and were admitted to the Royal Naval Hospital Haslar between 1991 and 1995. Males predominated (38 v 10) as did cases of deliberate self poisoning (31 v 17). The most common presenting feature was unconsciousness, which is an indication for hyperbaric oxygen and therefore reflects referral patterns. If patients had not recovered completely after one hyperbaric exposure further treatments were given. The initial hydrogen ion concentration of those requiring more than one treatment was significantly higher than those who recovered after the first treatment. The initial carboxyhaemoglobin (COHb) concentration showed only a trend to being higher in the multiple treatment group. Although metabolic acidosis is well recognised, its relationship to treatment requirements has not been shown previously. Initial COHb does not always correlate well with severity of poisoning which relates to the mechanism of toxicity of carbon monoxide: binding of carbon monoxide to the intracellular oxygen carrying proteins (for example cytochromes) rather than solely to haemoglobin. These findings are consistent with this mechanism and suggests that initial acidosis is a better predictor of treatment requirements and severity than initial COHb.

Acidosis, Respiratory↗
PubMed1999

Application of a time-resolved fluoroimmunoassay for the analysis of normal prion protein in human blood and its components.

BACKGROUND AND OBJECTIVES: To quantify the cellular isoform of prion protein (PrP(c)) in human blood using a new time-resolved dissociation-enhanced fluoroimmunoassay (DELFIA). MATERIALS AND METHODS: The DELFIA was optimised for human blood samples and applied to isolated cell and plasma fractions from blood donations. The physicochemical properties of PrP(c) were analysed. RESULTS: 26. 5% of blood PrP(c) was associated with the platelet fraction, 0.8% with polymorphonuclear leucocytes, 2.4% with mononuclear leucocytes, 1.8% with red cells and 68.5% with plasma (mean values from 4 processed donations). CONCLUSION: The majority of blood PrP(c) is found in the platelet and plasma compartments.

Antigens↗
PubMed1999

Motion sickness in public road transport: the relative importance of motion, vision and individual differences.

The relative importance of vehicle motion, a view of the road ahead and passenger characteristics in the causation of motion sickness in road transport has been investigated using survey data from 3256 coach passengers and measurements of coach motion. Overall, 28% of passengers said they felt unwell during coach travel. Prior experience of sickness, travel regularity and age were the factors most highly correlated with illness. Increased vehicle motion and poorer forward vision also correlated with illness. Little difference in illness was apparent with a good view of the road ahead, regardless of motion exposure, although vision alone was not sufficient to eliminate passenger sickness entirely. The results suggest that travel sickness could be significantly reduced by improved forward external vision and that improved forward vision may be particularly beneficial for individuals new to coach travel and for those who travel less often.

Adolescent↗
PubMed1999

Investigation of distal aortic compliance and vasodilator responsiveness in heart failure due to proximal aortic stenosis in the guinea pig.

Hypotension and syncope are recognized features of chronic aortic stenosis. This study examined vasomotor responses and dynamic compliance in isolated abdominal aortae after chronic constriction of the ascending aorta. Guinea pigs underwent constriction of the ascending aorta or sham operation. Sections of descending aorta were removed for studies of contractile performance and compliance. Dynamic compliance was measured using a feedback-controlled pulsatile pressure system at frequencies of 0.5, 1.5 and 2.5 Hz and mean pressures from 40 to 100 mmHg. Chronic (149+/-6 days) aortic constriction resulted in significant increases in organ weight/body weight ratios for left ventricle (58%), right ventricle (100%) and lung (61%). The presence of heart failure was indicated by increased lung weights, left ventricular end-diastolic pressure and systemic vascular resistance, reduced cardiac output and increased levels of plasma atrial natriuretic peptide (166%), adrenaline (x20), noradrenaline (106%) and dopamine (x3). Aortic rings showed similar constrictor responses to phenylephrine and angiotensin II, but maximal vasodilator responses to acetylcholine and isoprenaline were significantly increased (144% and 48% respectively). Dilator responses to sodium nitroprusside, forskolin and cromokalim were unchanged. Compliance of all vessels decreased with increasing pulsatile frequency and to a lesser extent with increased mean pressure, but were similar in aortic-constricted and control groups. Chronic constriction of the ascending aorta resulted in heart failure and increased vasodilator responses to acetylcholine and isoprenaline in the distal aorta while dynamic compliance was unchanged. We hypothesize that increased endothelium-mediated vasodilatation may contribute to hypotension and syncope in patients with left ventricular outflow obstruction.

Animals↗