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Biomedical subjects

A Carr

Publications and source records attributed to A Carr.

At least 19 recordsLinked to original sources

Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis in patients with AIDS.

OBJECTIVE: To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: Tertiary referral teaching hospital. PATIENTS: During a 3-year period after primary episodes of P. carinii pneumonia, 60 patients received trimethoprim-sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78 patients and intravenous in 17 patients) as secondary prophylaxis. RESULTS: No patient in the trimethoprim-sulfamethoxazole group and no patient seronegative for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36 (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A significant difference was seen in the time to development of toxoplasmic encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153 days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any group. CONCLUSIONS: Low-dose trimethoprim-sulfamethoxazole (four tablets per week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV-infected patients with previous P. carinii pneumonia. A prospective, randomized, controlled study is needed to further evaluate these findings.

Acquired Immunodeficiency Syndrome

Trimethoprim-sulphamethoxazole appears more effective than aerosolized pentamidine as secondary prophylaxis against Pneumocystis carinii pneumonia in patients with AIDS.

OBJECTIVE: We compared the efficacies of low-dose trimethoprim-sulphamethoxazole (TMP-SMX; one tablet: TMP, 160 mg, SMX, 800 mg, twice daily, twice a week) and aerosolized pentamidine (300 mg every 4 weeks) as secondary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV infection. DESIGN: A retrospective controlled study. SETTING: The study was performed at St Vincent's Hospital, Sydney, Australia, which is a tertiary referral university hospital. PATIENTS, PARTICIPANTS: Over a 4-year period, following primary episodes of PCP, 60 patients received TMP-SMX and 73 aerosolized pentamidine. Thirty-eight patients who received no secondary prophylaxis served as historical controls. MAIN OUTCOME MEASURES: The rate of and time to PCP relapse was recorded for patients receiving low-dose TMP-SMX, aerosolized pentamidine, or no prophylaxis. RESULTS: Only one (1.7%) patient in the TMP-SMX-treated group relapsed, compared with 31 (42.5%) of those in the aerosolized pentamidine group and 21 (55.1%) of those in the control group (P less than 0.0001). Median PCP-free survival times were greater than 1153 days in the TMP-SMX group, 496 days in the pentamidine group, and 265 days in the control group (P less than 0.0001 between all groups). The rate of or time to relapse was not influenced by CD4+ lymphocyte count at the start of prophylaxis, primary therapy of PCP, history of allergy to TMP-SMX, or zidovudine therapy during the period of secondary prophylaxis in any patient group. Both therapies were well tolerated, with three (5%) of those receiving TMP-SMX and four (5%) of those receiving pentamidine discontinuing therapy as a result of side-effects. CONCLUSIONS: Low-dose TMP-SMX appears to be more effective compared with aerosolized pentamidine as secondary prophylaxis against PCP in HIV-infected patients. Zidovudine was well tolerated by both groups, but did not influence the rate of or time to relapse.

Acquired Immunodeficiency Syndrome

How do home health nurses spend their time?

Of critical importance to the financial viability of any home health agency are its productivity standards for staff. The authors discuss the results of a study that analyzed staff time spent in direct patient care, documentation of that care, travel, and other activities, and how the resulting data influenced agency operations.

Chicago

New vectors in fission yeast: application for cloning the his2 gene.

We describe a new Escherichia coli vector (pON5) that allows positive selection for recombinant clones. In this plasmid, the bla gene from pBR322 is permanently active, whereas the neo gene from transposon Tn5 is repressed by the cI-encoded lambda repressor. When DNA is inserted into the Bc/I or HindIII restriction sites situated within the cI gene, the neo gene becomes transcribed from the lambda pR promoter. We have also made a Schizosaccharomyces pombe derivative of pON5 (= pON163) by introducing the fission yeast ars1 and ura4+ sequences. We show that this plasmid is capable of transforming Sc. pombe ura4 strains, as well as ura 3 strains of the distantly related budding yeast Saccharomyces cerevisiae. We have used pON163 for the construction of two fission yeast genomic libraries. From these gene banks clones were isolated that were able to complement fission yeast his2 mutants. Such plasmids could also rescue his4C mutants of Sa. cerevisiae, defective in the histidinol dehydrogenase activity of the multifunctional HIS4 gene product. Finally, we describe the plasmid pDW232 which is useful for functional analysis of fission yeast genes. It is a pGEM3 derivative adapted to fission yeast, carrying multiple cloning sites between the T7 and SP6 promoters, together with ars1 and ura4+ from Sc. pombe.

Cloning, Molecular

Allergic manifestations of human immunodeficiency virus (HIV) infection.

Drug allergy is the most common and significant allergic manifestation of HIV3 infection. Initially described in patients treated with SMX-TMP for PCP, allergy is now known to involve a multitude of drugs. The pathogenesis of, and risk factors for, allergy in HIV infection are poorly understood, although there is evidence suggesting that allergy is more common with advancing immunodeficiency. HIV-negative subjects with sulfonamide allergy may have drug-specific antibodies and drug metabolite-induced lymphocyte cytotoxicity, abnormalities that could partly explain the allergic mechanisms and which may have future diagnostic potential; these abnormalities have not been described in HIV-infected subjects. Therapy includes avoidance, suppressive agents such as corticosteroids, and desensitization, although the appropriate role for each is not entirely clear. Serum IgE levels have been shown to rise with progressive disease; those patients with higher levels may have a worse prognosis. The mechanisms of this rise are multifactorial, probably a combination of altered T-lymphocyte regulation of IgE synthesis and of production of specific IgE directed against microbial antigens.

Acquired Immunodeficiency Syndrome

Negative symptoms and reaction time in schizophrenia.

This study explored the association of negative symptoms and reaction time. Negative symptoms were specifically associated with reaction time slowing and variability in schizophrenics, but not in affective disorders. The finding of specificity did not extend to other measures of the deficit syndrome nor to motor performance. An abbreviated version of the negative symptom scale was especially effective in separating groups.

Adult

Voluntary motor performance in psychotic disorders: a replication study.

Voluntary motor performance was used to investigate the hypothesis of a continuum of psychosis from depression through schizophrenia. 43 schizophrenic, 36 schizoaffective, 50 major depressive, 20 manic, and 25 nonpsychotic patient controls were tested for tapping speed, finger dexterity, hand grip strength, and neuropsychological motor performance. Sex was included as an independent variable, and the effects of psychotropic drugs were evaluated. A continuum of motor dysfunction from depression through schizophrenia was not obtained. A measure of current psychotic symptoms was not associated with motor or neuropsychological performance. Motor performance was significantly worse in schizophrenic, schizoaffective, and psychotic affective disorders, when compared to nonpsychotic affective disorders. In this final analysis, psychoticism was defined by history. The results are discussed in terms of the hypothesis that psychoticism is a trait that is independent of diagnosis.

Humans

Antigen expression during development of the human hookworm, Necator americanus (Nematoda).

The accumulated and de novo synthesized antigens expressed by L3, L4 and adult Necator americanus, recognized by both the natural host, man, and the experimental host, the hamster, were identified by immunoblotting and immunoprecipitation analysis. Following infection of neonatal hamsters serum samples were taken on days 17, 35 and 117. Only serum taken 117 days after infection showed significant reactivity in immunoblotting experiments, recognizing adult epitopes of 30,000, 33,000, 48,000 and 69,000 mol. wt thereby suggesting that few accumulated antigens are shared between developmental stages. By contrast, immunoprecipitation analysis of metabolically labelled proteins suggested that L3 and in particular L4 larvae synthesize some antigens which comigrate with those synthesized and accumulated by adult worms. In addition, L4 larvae synthesize a 41,000 mol. wt excretory/secretory (ES) stage specific antigen. Parallel experiments using serum samples from infected humans, demonstrated that hamsters and man recognize many antigens of identical molecular weight. Notable in this respect are accumulated adult antigens of 30,000, 33,000, 48,000 and 69,000 and de novo synthesized antigens of 30,000, 33,000, 44,000, 46,000 and 69,000 mol. wt. Some individual human sera mainly recognized L3 antigens of 47,000-69,000 mol. wt in immunoblotting experiments whilst others simultaneously recognized adult epitopes. This differential recognition of developmental stages by individual human sera suggests that genetic or epidemiological factors are operative and warrants further study. Overall, these studies confirm the pronounced immunogenicity of Necator americanus in both man and an animal model and pave the way for analysis of the relevance of these antigens to field situations.

Animals

pp60c-src expression in transdifferentiating cultures of embryonic chick neural retina cells.

Chick embryo neural retinal cells transdifferentiate extensively into lens cells when cultured in Eagle's MEM containing horse and fetal calf sera (FHMEM). Such cultures express elevated levels of pp60c-src-associated tyrosine kinase activity relative to parallel cultures prevented from transdifferentiating by the addition of supplementary glucose (FHGMEM) or replacement of MEM by medium 199 (F199). Northern blotting and in vitro translation studies suggest that c-src mRNA levels are only slightly higher in late transdifferentiating (FHMEM) cultures as compared to parallel blocked (FHGMEM or F199) cultures. By immunocytochemical staining, we show that pp60c-src protein is largely localized in cell groups undergoing conversion into lens (i.e. expressing delta crystallin) in late FHMEM cultures. Initial studies of pp60c-src in chick lens tissues during development indicate that higher kinase activity is found in the epithelial cells relative to mature lens fibres. Thus pp60c-src may be expressed both during the differentiation of lens cells in vivo and during the transdifferentiation of neural retina cells into lens in vitro.

Animals

Identification of hookworm (Necator americanus) antigens and their translation in vitro.

During in vitro culture adult (day 35) Necator americanus synthesise a wide range of protein species many of which are excreted or secreted into the culture medium. Both post infection (day 117) hamster sera and sera from infected humans precipitate antigens of 15, 30, 33, 44, 46 and 69 kDa although individual human sera exhibit some variability in absolute specificity. In immunoblotting experiments antigens of 33 kDa are routinely recognised by human sera although two-dimensional gel analysis suggests that more than one polypeptide is involved. RNA isolated from adult worms direct the in vitro synthesis of numerous polypeptides possessing antigenic determinants recognised by sera from infected hamsters and humans. Post-translational modification of N. americanus encoded polypeptides is not, therefore, a prerequisite for antigenicity.

Animals

The recognition of antigens on the surface of adult and L4 Necator americanus by human and hamster post-infection sera.

The surface antigens of adult Necator americanus were recognized by post-infection hamster sera and resolved at molecular weight 93,000, 67,000, 46,000, 43,000, 32,000 and 25,000. L4 larvae in contrast had one major surface antigen, resolving at 93,000. These antigens were also recognized by a range of human sera, although on a differential basis. This suggests that the human sera tion. However, the results do indicate that the hamster model might be of immunological relevance to the human disease state, in that infected hamster recognized the full cuticular antigen spectrum of adult Necator. This, at least, gives the experimenter a convenient reference point from which to conduct further experiments incorporating parameters such as re-infection, anthelmintic treatment and genetic variability to study the effect of these modifications on the serological response.

Animals

Cloning, sequencing and transcriptional control of the Schizosaccharomyces pombe cdc10 'start' gene.

The cdc10 'start' gene from the fission yeast Schizosaccharomyces pombe has been cloned by rescue of mutant function. It is present as a single copy in the haploid genome. Hybridisation of the gene to Northern blots has identified a low abundance 2.7-kb polyadenylated RNA. Study of RNA extracted from cells both entering stationary phase and undergoing synchronous cell divisions suggests that commitment to the cell cycle is not controlled by regulation of cdc10 transcript level. DNA sequence analysis of the gene has identified an open reading frame capable of encoding a protein of mol. wt. 85 400. The putative cdc10 gene product shows no significant primary structure similarity with products of other fission and budding yeast cell cycle genes, or with other protein sequences in several databases.

Ascomycota

Fibroblast feeder layers inhibit differentiation of retinoic acid-treated embryonal carcinoma cells by increasing the probability of stem cell renewal.

The appearance of differentiated cells in embryonal carcinoma (EC) cultures can be inhibited by culturing the cells on fibroblast feeder layers. To determine whether or not feeder layers act by increasing the probability of stem cell renewal, growth and differentiation were monitored in cultures of F9 (subclone OTF9 -63) EC cells exposed to retinoic acid (RA) in either the presence or absence of feeder layers. By measuring the fraction of laminin-positive TROMA 1-positive or alkaline phosphatase-negative cells, it was determined that the frequency of differentiated cells in RA-treated F9 cultures was reduced by 70-80% when cells were cultured on fibroblast feeder layers instead of gelatin-coated dishes. Experiments in which EC cells were cultured in close proximity to a feeder layer demonstrated that cell-cell contact was required for maximal inhibition of differentiation. The probability of stem cell renewal was determined by measuring the number of colony-forming cells in RA-treated cultures as a function of time. Analysis of the data demonstrated that the probabilities of stem cell renewal were 0.5 and 0.25 during the first and second 48 h periods, respectively, following addition of RA for cells cultured without feeder layers. Cultures maintained on feeder layers exhibited a stem cell renewal probability of 0.72. Thus, feeder layers reduce the frequency of differentiated cells in RA-treated cultures by increasing the probability of stem cell renewal. Determining the mechanism by which feeder layers counteract the effect of a chemically defined differentiation inducer should help to uncover the processes that regulate the probability of stem cell renewal.

Animals