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Biomedical subjects

A Carr

Publications and source records attributed to A Carr.

At least 163 records · Page 9Linked to original sources

In vitro cytotoxicity as a marker of hypersensitivity to sulphamethoxazole in patients with HIV.

Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) in patients with HIV infection may be a result of either immune dysregulation, a direct cytotoxicity of the SMX-hydroxylamine metabolite (SMX-HA) (rather than SMX per se), or glutathione deficiency. We evaluated the in vitro cytotoxicity of SMX and SMX-HA to peripheral blood mononuclear cells (PBMC) of HIV-infected subjects to determine if the degree of in vitro cytotoxicity is associated with hypersensitivity, whether glutathione inhibits cytotoxicity, and whether in vitro cytotoxicity is predictive for the development of hypersensitivity. Given that fever is often a prominent feature of hypersensitivity, we also assessed whether SMX or SMX-HA could induce the in vitro production of IL-1 beta, IL-6 or tumour necrosis factor-alpha (TNF-alpha) by PBMC. The cytotoxicities of SMX and SMX-HA to PBMC were assessed in 45 HIV-infected patients with prior TMP-SMX therapy, and in eight HIV- controls. Twelve HIV-infected subjects were studied prospectively before primary Pneumocystis carinii pneumonia (PCP) therapy or rechallenge with TMP-SMX in previously hypersensitive subjects. Cytokine production was measured in four hypersensitive and two non-hypersensitive HIV-infected subjects, and three HIV-uninfected controls. The cytotoxicity of SMX-HA to PBMC was significantly greater in the 22 HIV-infected patients with prior hypersensitivity than both the 23 HIV-infected patients without hypersensitivity and the control group. Cytotoxicity was significantly reduced by glutathione only in the hypersensitive group. SMX did not induce cytotoxicity in any group. In 12 subjects studied prospectively, SMX-HA cytotoxicity was also significantly greater in those with subsequent hypersensitivity. Exposure of PBMC to SMX-HA resulted in a modest increase in the production of IL-6, IL-1 beta and TNF-alpha, although no major difference was detected between subjects with or without hypersensitivity. These data suggest that SMX-HA and glutathione deficiency are involved in the pathogenesis of hypersensitivity to TMP-SMX in HIV-infected patients, and that in vitro cytotoxicity could be useful in the diagnosis of hypersensitivity and predicting its likelihood.

Adult↗

Medial unicompartmental arthroplasty. A survival study of the Oxford meniscal knee.

One hundred twenty-one knees with medial compartment osteoarthrosis were treated by unicompartmental arthroplasty with the Oxford Knee. The strict selection criteria were (1) the presence of a functioning anterior cruciate ligament, (2) fully correctable deformity, and (3) full thickness of articular cartilage in the lateral compartment. The mean elapsed time from surgery was 44.4 months. One knee has required revision for a loose tibial component. The results at this stage are as acceptable as those of tricompartmental knee arthroplasty and better than those of high tibial osteotomy.

Aged↗

Prophylaxis of opportunistic infections in patients with HIV infection.

Prophylaxis of opportunistic infections in patients with human immunodeficiency virus (HIV) infection has been one of the major factors responsible for increasing patient survival. Secondary prophylaxis of most opportunistic infections is warranted, although in most instances the optimal therapy remains to be determined. Primary prophylaxis of opportunistic infections is an attractive concept, as the majority of opportunistic infections are reactivations of latent infections. Primary prophylaxis against Pneumocystis carinii pneumonia is both effective and necessary, but the role for primary prophylaxis against other infections is as yet unclear. Use of prophylactic agents requires careful study for determining the most effective and least toxic forms of prophylaxis that will allow for adequate concurrent antiretroviral therapy but will not induce resistant organisms.

AIDS-Related Opportunistic Infections↗

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↗

Avoidable causes of cancellation in elective orthopaedic surgery.

As part of an audit of clinical practice in an orthopaedic unit for elective surgery, a study was made of the causes of cancellation of operations. Despite careful liaison with general practitioners, and a booked admission policy, over 6% of patients were cancelled as unsuitable. The results of this study suggest that the number of cancellations on medical grounds would be reduced by closer liaison with general practitioners, and the establishment of preadmission clinics. Ensuring that only consultants book patients for surgery would also reduce the number of cancellations due to incorrect indications for surgery.

Appointments and Schedules↗

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↗