Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord

Previously we have shown that leukaemia inhibitory factor (LIF) potentiates the development of murine spinal cord neurons in vitro , suggesting that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and show here that the generation of neurons in cultures of embryonic day 10 spinal cord cells is inhibited by antibodies to the β subunit of the LIF receptor. Since there are more undifferentiated precursors in antibody-treated cultures than in control and LIF-treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival. In addition, the failure of LIF to support neuronal survival in the period immediately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inability to express class I major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an intermediary cell. LIF also appears to be involved in regulating the differentiation of astrocytes, since it increases the number of glial fibrillary protein (GFAP)-positive cells present in the cultures and since the spontaneous production of GFAP-positive cells is blocked by antibodies to the LIF β receptor. These findings suggest that LIF or related factors promote the differentiation of neural precursors in the spinal cord, but that they are not involved in preferentially promoting precursors down a specific differentiation pathway.     

Seasonality in the sudden infant death syndrome

Distinctive epidemiological features of the sudden infant death syndrome (SIDS) are its age at death distribution and pronounced winter excess. Whether or not these effects are independent of the month of birth of the infant is uncertain. We used a loglinear model to separate the effects of age at death, month of death and month of birth amongst 6229 infants who died from SIDS in England and Wales during the period 1979-1983. The results suggest that month of birth and month of death independently influence the risk of the infant dying from SIDS, the risk related to month of death being much greater.     

Importance of an immunodominant surface-exposed loop on outer membrane protein P2 of nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHI) frequently causes recurrent infections of the respiratory tract in humans. Previous indirect evidence suggested that a strain-specific immune response occurs following infection and that this immune response is directed at an immunodominant epitope on the bacterial surface. To test this hypothesis, mice and rabbits were immunized with whole cells of a strain of NTHI and the antiserum was characterized to identify the antigens to which antibodies were directed. All animals made a prominent antibody response to the loop 5 region of the P2 molecule, which is the major outer membrane protein. Rabbit serum showed complement-dependent bactericidal activity. Adsorption of the immune serum with the loop 5 fusion peptide removed bactericidal activity and also abolished reactivity to P2 detected by an immunoblot assay, an enzyme-linked immunosorbent assay, and a radioimmunoprecipitation assay. These data indicate that immunization with whole cells of NTHI results in a prominent antibody response which is directed at epitopes on the loop 5 region of the P2 molecule. Thus, a strain-specific immune response to NTHI occurs as a result of the expression of an immunodominant epitope on the P2 molecule.     

Effects of selective dopamine-1 receptor activation on intraocular pressure in man

The lack of specific agonists and antagonists has, until recently, precluded investigation of a role for dopamine receptors in the control of intraocular pressure. In the present study, we have examined the effects of fenoldopam, a novel selective dopamine1 (DA1) receptor agonist, on intraocular pressure, in eight healthy human volunteers. Fenoldopam, infused intravenously at 0.5 micrograms kg-1 min-1, increased intraocular pressure from 14.6 +/- 0.9 to 17.6 +/- 1.4 mmHg (P less than 0.05) while a control saline infusion had no effect. Pupil diameter and blood pressure did not change. In the same subjects, i.v. norepinephrine or angiotensin II both increased intraocular pressure--from 13.8 +/- 1.4- to 17.6 +/- 1.4 mmHg and from 13.4 +/- 1.3- to 17.5 +/- 1.7 mmHg respectively (P less than 0.05), and mean arterial pressure by about 20 mmHg. These data suggest that: (1) DA1 receptor activation can modulate intraocular pressure; (2) the intraocular pressure effects of the DA1 receptor agonist, fenoldopam, are independent of changes in systemic blood pressure, in contrast to those of norepinephrine or angiotensin II where intraocular and systemic blood pressures increase in parallel; (3) the ability of a DA1 receptor antagonist to lower intraocular pressure merits investigation.     

The effects of cysteamine on the upper gastrointestinal tract of children with cystinosis

The purpose of this study was to evaluate the effects of cysteamine on gastric acid output and serum gastrin levels in children with nephropathic cystinosis. We studied four children with nephropathic cystinosis receiving a dose of free base cysteamine of 14.35 mg/kg four times a day (range 12.30 – 18.80 mg/kg). Gastric acid was measured for the hour before and after administration of the medication. Serum gastrin levels were obtained at 0, 30, 60, and 90 min following the medication. Gastrointestinal anatomy was evaluated by endoscopy and biopsy. Following administration of the medication, all subjects showed an increase in gastric acid output. Mean acid output increased from 0.79 to 2.22 mEq/h. Mean gastric acid output adjusted for body weight increased from 0.03 to 0.09 mEq/kg per hour. Following administration of the medication, all subjects showed an increase in serum gastrin. The mean increase above the base value was 38.3 pg/dl. Two of the four subjects demonstrated visual and histological evidence of inflammation. Cysteamine has a marked effect on gastric acid production and serum gastrin, even at the dose used in children with nephropathic cystinosis. The clinical effect of this acid production is unknown but may be significant. Received February 13, 1996; received in revised form February 25, 1997; accepted February 27, 1997     

Bilateral facial paralysis: a case presentation and literature review.

Bilateral facial paralysis is a diagnostic challenge, which may manifest itself as either a simultaneous or alternating form, occurring in 0.3-2.0% of patients that present with facial paralysis. The differential diagnosis of facial paralysis includes congenital, traumatic, neurologic, infectious, metabolic, neoplastic, toxic, iatrogenic and idiopathic etiologies. While idiopathic facial paralysis is the most common diagnosis, a comprehensive evaluation must be completed prior to this diagnosis in patients with bilateral facial paralysis. A representative case of simultaneous bilateral facial paralysis is presented. The literature is reviewed and discussed. A diagnostic protocol for the evaluation of bilateral facial paralysis is proposed. Bilateral facial paralysis requires a thorough evaluation and may prove to be a diagnostic dilemma.     

The complications of immobility in the elderly stroke patient.

BACKGROUND: Approximately 500,000 persons in the United States suffer a stroke each year; the majority of these individuals are 65 years of age or older. The neurological impairment occurring as the result of stroke can lead to both acute and chronic disability. Further medical complication and disability are often the result of immobility-related illness that occurs while the patient is still in the hospital. METHODS: A MEDLINE search for articles published from 1980 to 1990 was made using the key words immobilization and stroke rehabilitation. The bibliographies of these articles, key rehabilitation and geriatric textbooks, the bibliographies of these textbooks, and the authors' personal files were also sources of information. RESULTS AND CONCLUSIONS: Immobility-related medical complication and disability can be substantially reduced by identifying risk factors and applying preventive measures. As long-term providers of medical care, family physicians are in a position to devise a preventive care plan for immobility-related disability and to appreciate the beneficial effects of such a plan on patient outcome.     

CT-guided brachial plexus biopsy.

We describe a technique for conducting a CT-guided biopsy of the brachial plexus region, report two illustrative cases, discuss potential complications, and conclude that, in selected cases, biopsy of lesions in the region of the brachial plexus can be performed safely with CT guidance.     

Spina Bifida: The Transition into Adulthood Begins in Infancy

Many concerns surround the preparation of a person with spina bifida for a successful transition into adult life and responsibilities. A model of intervention must be based on developmental concerns and timely issues from infancy through all stages of development to young-adult life. This article discusses, within a developmental framework, issues of transition in relation to physical, social, emotional, and educational/vocational needs; it also presents a conceptual framework for the transition into adulthood. Guidelines were developed by incorporating expected outcomes of people with spina bifida and using a philosophical framework that encompasses the achievement of a balance among dependence, independence, and interdependence. This model is based on developmental issues from infancy through all stages of development to young-adult life. Using this framework for care, the rehabilitation nurse can feel confident that the needs of clients with spina bifida and similar chronic conditions are being met.     

Sample size determination for an exponential survival model with an unrestricted covariate

We derive formulae for estimating sample size and power for detecting the effect of an unrestricted covariate on survival time. These are useful in designing survival studies with different patterns of recruitment and follow-up when survival time is exponentially distributed. We use the asymptotic covariance matrix, conditional expectation and Taylor's expansion techniques to develop these formulae. Computer simulations indicate that the asymptotic approximations used in developing the formulae are good over a range of parameter values and different patterns of recruitment and follow-up that are relevant to survival studies.