Search

The technique of in situ hybridization with tritiated RNA probes was used to study the expression of the 68 kDa neurofilament (NF68) gene and the superoxide dismutase-1 (SOD-1) gene in the brains of Alzheimer's disease (AD) patients. Messenger RNA (mRNA) for these proteins was localized and quantified in single cells of formalin-fixed, paraffin-embedded sections of 4 pairs of AD and Huntington's disease (HD) brains from patients matched for age at death and autopsy interval. The cerebellar cortex and hippocampal CA1 and CA2 regions were compared in these two groups of subjects, since in AD the CA2 region of the hippocampus and the cerebellum have been found to be relatively unaffected by the Alzheimer process in comparison to the hippocampal CA1 region. The amount of NF68 mRNA was reduced by approximately 50% in pyramidal cells of both the CA1 and CA2 of AD hippocampus (P less than 0.001), and by 15% in the Purkinje cells of AD cerebellum (P less than 0.05) relative to that of the HD individuals. SOD-1 mRNA was reduced by about 22% in the CA1 of AD brains (P less than 0.001) with no corresponding reduction in the CA2, and by only 5% in the AD cerebellum (P greater than 0.5). The paired design of the study suggests that these results are not simply attributable to the effects of autopsy interval or the agonal process in each patient's death.

The Gram negative organism, Pseudomonas aeruginosa, is often found in the lungs of patients with cystic fibrosis and other forms of severe bronchiectasis, where it secretes a number of extracellular toxins including the mono- and dirhamnolipids. The principal monorhamnolipid from P. aeruginosa has previously been identified as rhamnosyl-3-hydroxydecanoyl-3-hydroxydecanoate (Rh-C10.C10). A number of related mono- and dirhamnolipids have been purified from cultures of a clinical isolate of P. aeruginosa and identified by fast atom bombardment and electron impact mass spectrometry: these contain the 3-hydroxyoctanoyl-3-hydroxydecanoate (C8.C10) and 3-hydroxydecanoyl-3-hydroxydodecanoate (C10.C12) homologues. Structural isomers were also present where the order of the lipid linkage was transposed (Rh-C10.C8 and Rh-C12.C10). Unsaturated mono- and dirhamnolipids containing the 3-hydroxydecanoyl-3-hydroxydodec-5-enoate (C10.C12:1) lipid were also present.

Serum tests of thyroid function were compared in Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD). Relative to control individuals, DS patients had, overall, lower mean total T4 (P = 0.070) and T3f (P = 0.015), higher T3U (P = 0.013) and TSH (P = 0.020), no difference in free T4, and higher thyroid antithyroglobulin (ATA) (P = 0.033) and antimicrosomal autoantibody (AMA) titres (P = 0.0097). Similar trends were apparent in DS males and females, and in DS patients off all drugs. In an analysis of case/control pairs with corrections for age and sex, DS patients with AD manifestations (n = 9) had significantly lower T3 (P = 0.029) and higher AMA (P = 0.043) than paired control individuals, whereas DS patients without AD manifestations (n = 20) had significantly lower T3 (P = 0.013) but higher ATA (P = 0.0065). T3 was significantly lower in the DS patients with AD manifestations than in the unaffected (P = 0.0013). These data suggest that autoimmune thyroiditis associated with a mild "subclinical" form of hypothyroidism is common in adult DS patients and more pronounced in patients with AD manifestations than in those without. This "subclinical" hypothyroidism may contribute to cognitive deficits in ageing DS patients.

In general, there is a low incidence of HIV infection in members of school communities. Moreover, all available evidence supports the conclusion that HIV is not transmitted by the everyday contacts which occur in family, social, employment and educational settings. Despite this, the presence, in a school community, of persons infected with HIV or who have an HIV related disease have been perceived by some as presenting a threat to their children's, and even to their own health and well-being, which, in turn, has led to serious conflicts between various participants in that community. Experience, however, has shown that the fears of many persons and the risks of conflict and confrontation can be minimized, if not negated, if a school board has adopted policies and procedures in relation to HIV/AIDS. Such policies and procedures must be based on current medical knowledge and clearly identified ethical and legal principles, including identification of the rights, interests and needs of all persons and development of appropriate analyses, especially where these are required to resolve conflicts. In this text, educational authorities and their advisors are provided both with a comprehensive model HIV/AIDS policy, and a commentary which examines, amongst other matters, the fundamental ethical and legal considerations which have guided its formulation and the justifications for each of the principles contained therein.

We have tested whether two local anaesthetics, in the lumen of cat trachea in vivo, would block the stimulation of mucus secretion by parasympathetic nerves without altering its stimulation by a cholinergic drug. Lignocaine, 4.3-43 mM (0.1-1%) in Krebs-Henseleit, increased the output of mucus macromolecules. It abolished secretion in response to vagus nerve stimulation, but also diminished the effect of 5 microM pilocarpine. Tetrodotoxin, 50 microM, abolished vagal control of secretion without inhibiting pilocarpine's action or changing resting secretion. Though lignocaine blocks nerve-mediated secretion, its action is not simply on nerve conduction. In contrast, the effect of tetrodotoxin may be restricted to the blocking of nerves.

A recent investigation, using a human genomic probe, has indicated that the 68,000 dalton neurofilament gene (NF68) is on the short arm of chromosome 8. We have used a murine cDNA probe on 65 metaphase spreads in situ to localize the human NF68 gene to 8p21 (20/370 grains; p less than 0.0001). In addition, we have found secondary hybridization sites at the centromeric region of chromosome 2 and the long arm of chromosome 7, which are putative loci for other intermediate filaments.

Three cases of severe falciparum malaria with high parasitaemia, one of them complicated by disseminated intravascular coagulation, were treated with exchange transfusion in addition to conventional chemotherapy. All three made a good recovery. There are few previous reports of this treatment which deserves wider attention and further assessment.

The title, 'justice across the generations', is reminiscent of expressions such as 'hands across the seas'. The latter is, of course, impossible in reality, but it symbolizes friendship between persons in far-flung lands. Is 'justice across the generations', likewise, no more than a hopeful metaphor, or is there, or at least should there be, some concrete reality to it? If so, what is, or should be, the substance of that reality? This text consists of some free association reflections, principally in the context of health care and mainly in the form of questions, on the concepts proclaimed in the title, namely, justice, across and generations, and what relevance these might have for our present and future societies.

Subjecting 9-day-old quail embryos to an elevated temperature in ovo causes limb, breast, and brain tissues to shift their patterns of protein synthesis from the production of a broad spectrum of different proteins to the new and (or) enhanced synthesis of a small number of heat-shock proteins (HSPs). The HSPs synthesized by undifferentiated breast tissue in ovo (relative masses (Mrs) 88 000, 82 000, 64 000, and 25 000) are similar to those synthesized by explanted breast tissue or by primary cultures of breast myoblasts heat-shocked in culture. Heat-shocked, 120-hour-old myotube cultures synthesize HSPs similar to those detected in heat-shocked myoblasts except that myotubes also exhibit enhanced synthesis of a 55 000 dalton polypeptide and little or no synthesis of a 25 000 dalton HSP; the failure to thermally induce a 25 000 dalton polypeptide in myotubes is related to the fused nature of these cells rather than to their state of differentiation. Myoblasts, as well as myotubes, cultured in the presence of elevated amounts of arsenite, copper, or zinc also synthesize new and (or) enhanced amounts of polypeptides with isoelectric points and immunochemical properties similar to the 25 000 and 64 000 dalton HSPs. However, elevated levels of these metal ions fail to stimulate new and (or) enhanced synthesis of other HSP-like proteins. These results demonstrate that, although the protein synthetic response of myogenic cells to chemical and thermal stress may be similar in some respects, a number of the synthetic responses are clearly different.

The susceptibility of Legionella pneumophila to a new quinolone, fleroxacin, was studied in both an extra- and an intracellular system. The activity of fleroxacin was compared with that of erythromycin, cefoxitin, and rifampicin. In the extracellular system, erythromycin inhibited while cefoxitin killed the organism. Extracellularly, fleroxacin performed similarly to cefoxitin. Rifampicin was initially bactericidal for L. pneumophila but resistant bacteria emerged at 48 h. The Horwitz monocyte model was used for studies of intracellular antimicrobial activity. At ten times the MIC, cefoxitin did not inhibit intracellular L. pneumophila. Fleroxacin was as active as erythromycin and rifampicin in inhibiting intracellular L. pneumophila. No intracellular, rifampicin-resistant L. pneumophila emerged. Addition of rifampicin to cefoxotin, erythromycin or fleroxacin provided neither synergy nor antagonism.

Recent success in overcoming rejection of transplanted organs has led to a much greater demand for organs from donors and to a reconsideration of mechanisms for increasing the availability of organs from cadavers. In the latter respect the two basic systems are "contracting-in" and "contracting-out". Each system has different benefits and harms, and it is a value judgement that should be adopted. However, both systems raise legal, ethical and practical issues that must be addressed if organs for transplantation are to become available to all who need them.

Susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA, n = 32), methicillin-sensitive S. aureus (MSSA, n = 32), and S. epidermidis (SE, n = 24) were determined to fleroxacin, amifloxacin, ciprofloxacin, difloxacin, enoxacin, norfloxacin, and ofloxacin. All organisms were isolated from the blood of patients with infective endocarditis. MRSA and MSSA MIC90s were less than 1.0 mg/l of fleroxacin, ciprofloxacin, difloxacin, and ofloxacin while amifloxacin and norfloxacin produced MIC90s of less than 2.0 mg/l and enoxacin MIC90s of less than 4.0 mg/l. For S. epidermidis MIC90s were less than 1.0 mg/l of all quinolones except amifloxacin whose MIC90 was less than 2.0 mg/l. Two strains from each staphylococcal group were used in time-kill trials performed with all seven quinolones. Within 8 h, all quinolones colony counts were decreased by one log. At 24 h, most quinolones decreased MRSA, MSSA, and SE colony counts by two to four logs; however, exceptions were found with (1) difloxacin, enoxacin, and norfloxacin against MRSA, (2) ciprofloxacin and enoxacin against MSSA, and (3) ciprofloxacin against SE in which all colony counts increased one to three logs in 24 h. When quinolone time-kill trials did not show a decrease in colony counts at 24 h, the MIC's for the 24 h growth showed a four- to 250-fold increase when compared with pre-trial MICs. No selection or emergence of resistant organisms was found with fleroxacin, amifloxacin or ofloxacin.