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.     

Impaired Glucose Tolerance in Pregnancy - Is It of Consequence?

Summary: This study was done to determine if impaired glucose tolerance in pregnancy was associated with increased maternal and neonatal morbidity and if so, whether the increased morbidity was due to the confounding factors of increased maternal age and maternal obesity. It was a retrospective analysis to compare 944 women with impaired glucose tolerance (IGT) in pregnancy with 10,065 women without abnormal glucose tolerance. The incidence of impaired glucose tolerance in pregnancy was 8.6% in this study. Even when maternal age and obesity were excluded, the IGT group had significantly higher risks of labour induction (relative risk, RR, 1.15); Caesarean section (RR: overall 1.43, elective 1.72, emergency 1.31); Caesarean section for dystocia/no progress (RR 1.60); macrosomia (RR 1.69,1.76,1.61 for birth-weight =97th, 95th, 90th percentiles respectively) and shoulder dystocia (RR 2.84) when compared to the nondiabetics (NDM). The risks of hypertensive disease (RR 1.22) and Caesarean section for fetal distress/thick meconium-stained liquor (RR 1.53) were also higher in the IGT group but these increases were not statistically significant when maternal age and obesity were excluded. There was no significant difference in the rates of low Apgar scores at 1 and 5 minutes between the 2 groups.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Ultrastructural identification of cholinergic neurons in the external cuneate nucleus of the gerbil: acetylcholinesterase histochemistry and choline acetyltransferase immunocytochemistry

Summary Using acetylcholinesterase histochemical and choline acetyltransferase immunocytochemical localization methods, this study has provided conclusive evidence for the existence of cholinergic neurons in the external cuneate nucleus of gerbils. By light microscopy, both acetylcholinesterase and choline acetyltransferase labelling was confined to the rostral portion of the external cuneate nucleus. Ultrastructurally, acetylcholinesterase reaction products were found in the nuclear envelope, cisternae of rough endoplasmic reticulum and Golgi saccules of some somata and large dendrites as well as in the membranes of small dendrites, myelinated axons and axon terminals. These neuronal elements were also stained for choline acetyltransferase; immunoreactivity was associated with nuclear pores, nuclear envelope, perikaryal membrane and all the membranous structures within the cytoplasm. Of the total choline acetyltransferase-labelled neuronal profiles analysed, 79% were myelinated axons, 15% dendrites, 4% somata and 2% axon terminals. The immunostained axon terminals consisted of two types containing either round (Rd type; 62.5%) or pleomorphic (Pd type; 37.5%) vesicles. Both were associated directly with choline acetyltransferase-positive dendrites. In contrast to the paucity of choline acetyltransferase-labelled axon terminals, numerous choline acetyltransferase-positive myelinated axons were present. It may thus be hypothesized that most, if not all, of the external cuneate nucleus cholinergic neurons are projection cells; such cells may give rise to axonal collaterals which synapse onto their own dendrites for possible feedback control. Choline acetyltransferase-positive dendrites were contacted by numerous unlabelled presynaptic boutons, 60% of which contained round or spherical synaptic vesicles (Rd boutons) and 40% flattened vesicles (Fd boutons), suggesting that these neurons are under strong inhibitory control. The preferential concentration of cholinergic components in the rostral external cuneate nucleus may be significant in the light of the highly organized somatotopy in the external cuneate nucleus and its extensive efferent projections to medullary autonomic-related nuclei. Our results suggest that the cholinergic neurons may be involved in somatoautonomic integration.     

CORRELATION OF IMMUNOLOGICAL SURFACE ANTIGENS WITH SURVIVAL IN DIFFUSE LARGE CELL LYMPHOMA

The prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty-eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA-DR (p=0·01) and normal levels of CD8 (p=0·04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA-DR in determining the prognosis of patients with diffuse large cell lymphoma.     

Assessment of nutritional status in children with cystic fibrosis: conventional anthropometry and bioelectrical impedance analysis. A cross-sectional study in Dutch patients

BACKGROUND: Assessment of nutritional status in children with cystic fibrosis (CF) is clinically relevant. Methods to measure nutritional status should be reliable and non-invasive, and reference values should be available. AIM: To compare weight and height measurements and measurements of specific body compartments in children with CF. METHODS: In a cross-sectional survey of 58 children with CF (28 females), we compared height and weight (expressed as: weight-for-height, body mass index (BMI), height-for-age and weight-for-age) with fat mass (skinfold sum (SFS)), muscle mass (upper arm circumference (UAC)) and bioelectrical impedance analysis (BIA). Results were expressed as Z-scores, using Dutch reference values. RESULTS: BMI and weight-for-height were within the normal range (mean Z-score (range): -0.13 (-1.5, 2.7) and -0.02 (-1.7, 2.8)). Weight and height corrected for age were below normal (mean Z-score (range): -0.79 (-2.4, -0.05) and -1.2 (-2.8, 1.4) (P<0.01)). Lean body mass by skinfold sum (LBM(sfs)), UAC and BIA were also significantly below reference values (mean Z-score (range): -0.9 (-2.2, 1.8), -0.95 (-2.4, 1.8) and -1.1 (-3.6, 1.0) (P<0.01)). Lean body mass (LBM) by BIA correlated with LBM(sfs). BIA systematically underestimated LBM in both CF patients and in control subjects. CONCLUSION: Nutritional status of children with CF must be evaluated, using age-corrected weight and height expressed in Z-score. LBM estimated by SFS, UAC and by BIA appear to be useful, although longitudinal studies in CF children should be performed to evaluate their clinical significance in detecting changes in nutritional status.     

Nonablative dermal remodeling with a 585-nm, 350-microsec, flashlamp pulsed dye laser: clinical and ultrastructural analysis.

BACKGROUND: A nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser is currently being used for the treatment of rhytides. OBJECTIVE: To analyze both clinical rhytid improvement and electron microscopic evidence of ultrastructural changes after treatment with a nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser. RESULTS: At 6 months after two treatments, 40% of the treated subjects noted mild improvement in rhytid appearance. Nontreating physician evaluation revealed some degree of improvement in 50% of the treated subjects. Mild improvement in quality and texture of the skin was also reported by 50% of the subjects. Electron microscopic evaluation showed ultrastructural changes that are consistent with new collagen formation. CONCLUSION: Treatment with a nonablative 350-microsec, 585-nm, flashlamp pulsed dye laser can lead to both clinical and electron microscopic evidence of improvement in photo-damaged skin.     

Comparative double-blinded study between mupirocin and tetracycline ointments for treating skin infections

A double-blinded study was conducted to compare the effects of mupirocin and tetracycline ointments in the treatment of skin infections. 111 patients were available for clinical assessment, of which 53 were treated with mupirocin and 58 treated with tetracycline. Clinically, both groups were improved, and there was no significant difference. Bacteriological assessment however revealed a better response to mupirocin. Staphylococcus aureus and Streptococcus pyogenes were the most common organisms isolated. 99% of Staphylococci were sensitive to mupirocin compared with 61% to tetracycline and 29% to penicillin G. 57% of Group A beta haemolytic Streptococci were resistant to tetracycline compared to 14% to mupirocin. Gram-negative organisms were mostly resistant to both preparations. No side effects were observed in both treatment groups. This study suggests that mupirocin is a safe and effective topical preparation for treating most of our common skin infections.     

Audit of 149 consecutive carotid endarterectomies performed by a single surgeon in a district general hospital over a 12-year period.

Carotid endarterectomy has been established by two large randomised controlled trials (European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET)) as an important surgical procedure for the prevention of ischaemic strokes in patients presenting with transient cerebral ischaemia or non-disabling strokes attributable to severe ipsilateral carotid artery stenosis. The operation carries significant risk of death and stroke and it has been advocated by some that carotid endarterectomy should only be performed in a small number of designated regional centres in order to achieve good surgical results. It is doubtful that the regional centres alone can cope with the increasing numbers of patients requiring carotid endarterectomy and there is therefore a requirement for the procedure to be carried out by vascular surgeons in district general hospitals. It is important that surgical results are audited to ensure that comparable outcomes are achieved. We present an audit of our experience of carotid endarterectomy since 1981. A total of 149 consecutive carotid endarterectomies were performed by a single surgeon with a special interest in carotid surgery. The results are comparable to ECST with a 30-day mortality of 0% and an overall 30-day stroke rate of 5.7% (major strokes) for patients with severe, ie 70-99%, ipsilateral carotid artery stenoses. We have shown that carotid endarterectomy is an operation that can be performed safely and with good results by suitably trained surgeons in district general hospitals.