T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates

Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four years after three newborns with this disease were given infusions of transduced autologous umbilical cord blood CD34+ cells, the frequency of gene-containing T lymphocytes has risen to 1-10%, whereas the frequencies of other hematopoietic and lymphoid cells containing the gene remain at 0.01-0.1%. Cessation of polyethylene glycol-conjugated adenosine deaminase enzyme replacement in one subject led to a decline in immune function, despite the persistence of gene-containing T lymphocytes. Thus, despite the long-term engraftment of transduced stem cells and selective accumulation of gene-containing T lymphocytes, improved gene transfer and expression will be needed to attain a therapeutic effect.     

Efficacy and safety of inhaled Salmeterol (Serevent) as maintenance therapy for asthma in Nairobi

An open study to assess the efficacy and safety of 50 micrograms inhaled Salmeterol (Serevent) administered twice daily as maintenance therapy for asthma was undertaken by the Respiratory Diseases Research Unit (RDRU) in Nairobi between August and October, 1992. Salmeterol (Hydroxynaphthoate) is a long acting selective beta-2-agonist. Seventy-three adult patients recruited at Kenyatta National Hospital underwent a two weeks treatment period during which they were assessed over three visits. At Visit 1, eligibility was confirmed, baseline lung function indices measured, the study drug introduced and all the previous medications withdrawn. After treatment for one week (Visit 2) and two weeks (Visit 3), lung function indices were measured again and subjective patients' and physicians' assessments of efficacy documented. Patients with obstructive ventilatory defect (OVD) at baseline had significant improvement in their lung function compared to those without at the end of the treatment period. A significant number of patients reported decreased number of nocturnal awakenings and increased tolerance to physical activity. Cough, headache and itchy throat were adverse events possibly related to the use of Salmeterol. The patients treated with Salmeterol gained improved control of their asthma symptoms. The drug offers a convenient dose schedule and we recommend its use for maintenance therapy for mild to moderate asthma.     

Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells

Mycobacterium tuberculosis infects one-third of the world's human population. This widespread infection depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. DNA sequences of M. tuberculosis have been cloned; these confer on a nonpathogenic Escherichia coli strain an ability to invade HeLa cells, augment macrophage phagocytosis, and survive for at least 24 hours inside the human macrophage. This capacity to gain entry into mammalian cells and survive inside the macrophage was localized to two distinct loci on the cloned M. tuberculosis DNA fragment.     

Single-case designs in the modification of smoking

Hepatic echo-angiostructure: echo-anatomical study of the intraparenchymatous canal With a suitable technique (real time, grey scale) hepatic ultrasonography is able to display intraglandular ductal elements: portal veinous network, supra-hepatic veinous network, and, if enlarged intrahepatic biliary tree. A careful echoanatomic study is necessary to identify the enlarged biliary network in case of obstructive jaundice; such a study is also necessary not to confuse normal ductal structures, insufficiently displayed, with pathological reflections - a rather frequent hazard with conventionnal techniques.     

An assessment of the 1982 traffic fatality decrease

United States traffic fatalities dropped dramatically from 49,301 in 1981 to an estimated 43,721 in 1982. Fatalities are at their lowest level in 20 yr, and fatalities per mile of travel are the lowest ever recorded. A decrease of similar magnitude occurred only in 1974, when the oil crisis, the national 55 mph speed limit, and depressed economic conditions disrupted the nation's driving habits. In 1982 the potential explanations are more difficult to observe and test. This paper examines several factors which may have contributed to the 1982 changes, including alcohol programs, occupant restraint use, demographic shifts, economic conditions, and travel patterns. Each factor's effect is assessed, though available data do not permit precise quantification. Implications of these findings for 1983 and beyond are discussed.     

Structural and biochemical changes in lungs of 3-methylindole-treated rats

This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE). MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L. In rabbits treated with a single-dose i.v. regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001). Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug. From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase-positive and methicillin-resistant S. epidermidis infection; some enzyme-resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S. epidermidis infection; the combination of co-amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model.     

Female choice and manipulations of forceps size and symmetry in the earwig Forficula auricularia L

Nutrition influences the reproductive axis via alteration of gonadotrophin secretion. However, a link between nutrition and the secretion of GnRH, which drives the axis, has yet to be established. The aim of the present study was to measure the change in the concentrations of metabolic substances in the cerebrospinal fluid of adult male sheep offered a diet designed to maintain constant gonadotrophin secretion (Group M; n = 6), or a diet known to increase gonadotrophin secretion (Group M + L; n = 6). On days 1, 3 and 10 of the dietary treatments, cerebrospinal fluid and jugular blood were sampled and analysed for metabolic fuels (glucose, amino acids and free fatty acids) and metabolic hormones (insulin, insulin-like growth factor I, GH, prolactin, cortisol and the thyroid hormones). On day 11 of the dietary treatment, LH pulse frequency and mean FSH concentrations in Group M + L had increased relative to Group M and to day 0. Plasma concentrations of prolactin and insulin on days 3 and 10, and glucose and insulin-like growth factor I on day 10, were higher in Group M + L than in Group M, but only cerebrospinal fluid concentrations of insulin, glucose and certain amino acids were affected by the dietary treatments on days 3 and 10. Cerebrospinal fluid, but not plasma, concentrations of aspartate, tyrosine, cystine, phenylalanine and arginine on day 3, and glutamine, gamma-aminobutyric acid, threonine, alanine on days 3 and 10, were higher in Group M + L relative to Group M. On day 10, plasma and cerebrospinal fluid concentrations of arginine, phenylalaine, proline, tyrosine, methionine and phosphoserine, but only the plasma concentrations of linoleic acid, aspartate and serine, were higher in Group M + L than in Group M. Concentrations of triiodothyronine, thyroxine, and cortisol in plasma and cerebrospinal fluid were not affected. These results show that the nutritional stimulation of gonadotrophin secretion is accompanied primarily by fluctuations in plasma and cerebrospinal fluid concentrations of insulin and certain amino acids, which suggests that, when nutritional status is improved, insulin, amino acids and possibly glucose interact to modulate GnRH secretion.