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Biomedical subjects

G X McLeod

Publications and source records attributed to G X McLeod.

9 recordsLinked to original sources

Collaborative management of HIV infection in the community: an effort to improve the quality of HIV care.

Our hospital led a multidisciplinary community team to improve the quality of care delivered to HIV-infected clients utilizing a disease management approach in a US metropolitan community of 150,000 people. Community needs assessment and client and community surveys were used to define the problems. Patient care flowcharting and the creation of an electronic patient database facilitated patient tracking across the entire community. Clinical guidelines and a consultation and referral immunology clinic standardized care practices. Measurable improvements in the quality of care were noted in multiple areas. Flowchart completion rates rose from 44% to 100%; medication adherence assessment rose from 82% to 100%; immunization rates rose from a mean of 72% to a mean of 87%; PPD screening rose from a low of 35% to a high of 87%; perinatal transmission rates fell from 31% to 4%; and Emergency Department utilization decreased. Two essential components of the effort were the establishment of a full-time leadership position in the form of a clinical nurse practitioner and the creation of an electronic database with flowcharting to standardize the measurement, delivery and tracking of care. The programme has become an example of successful disease management through hospital-community collaboration.

Adult↗

Candida osteomyelitis and diskitis after spinal surgery: an outbreak that implicates artificial nail use.

Postoperative wound infection after laminectomy is uncommon. In February 1997, 3 patients were confirmed to have postlaminectomy deep wound infections due to Candida albicans. No similar case had been seen during the previous 10 years. The infections were indolent, with a mean time from initial operation to diagnosis of 54 days (range, 26-83 days). All patients were successfully treated. Pulsed-field gel electrophoresis revealed the Candida isolates to be identical. A case-controlled study and medical record review revealed that a single operating room technician scrubbed on all 3 infected case patients but on only 32% of the uninfected controls. The technician had worn artificial nails for a 3-month period that included the dates of laminectomy site infections, and C. albicans was isolated from her throat. She was treated with fluconazole and removed from duty. No subsequent cases have occurred during the ensuing 3 years. Artificial nails are known to promote subungual growth of gram-negative bacilli and yeast. This may be clinically relevant, and hospitals should enforce policies to prevent operating room personnel from wearing artificial nails.

Adult↗

Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. The RV43 Study Group.

Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross-resistance to other similar dideoxynucleoside agents which contain a 3'-azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0-fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates.

AIDS-Related Complex↗

Zidovudine: five years later.

Zidovudine, a nucleoside analog, was the first agent proved to be effective in the management of human immunodeficiency virus type 1 (HIV-1) infection. After demonstration of zidovudine's in-vitro activity against HIV-1 in 1985, the drug was rapidly evaluated in phase I and phase II clinical trials and was found to be effective in decreasing both mortality and the incidence of opportunistic infections in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex; the drug was also found to have a substantial but tolerable toxicity profile. Since the licensure of zidovudine in 1987, an intensive clinical research effort has established the drug's efficacy in the prevention of disease progression in asymptomatic and mildly symptomatic HIV-infected persons and has established the success of lower-dose therapy in patients at all stages of disease. The current recommendation is to use zidovudine at a dose of 500 to 600 mg/d in both symptomatic and asymptomatic persons with CD4 counts of less than 500/mm3. The major toxicities of anemia and neutropenia are less frequent at the lower doses presently used and can be managed by dose reduction or by use of hematopoietic growth factors. The inexorable disease progression seen despite zidovudine therapy and the isolation of clinical strains of HIV-1 resistant to zidovudine in vitro highlight the limitations of prolonged monotherapy with this agent. Although alternative dideoxynucleoside agents (for example, didanosine [dideoxyinosine and zalcitabine dideoxycytidine]) are available for the management of HIV-infected persons, zidovudine remains the cornerstone of antiretroviral therapy. Current research efforts are directed at elucidating the clinical relevance of zidovudine resistance and studying regimens in which zidovudine is used in combination with other agents. This latter approach holds great promise for improving efficacy, limiting toxicity, and perhaps preventing the emergence of viral resistance. For the forseeable future, zidovudine will continue to play a role in the development and in our understanding of antiretroviral therapy.

Clinical Trials as Topic↗

Treatment of HIV infection: the antiretroviral nucleoside analogues. Nucleoside analogues: combination therapy.

Combination antiretroviral therapy is an important development in the management of HIV infection. AZT with ddC is the first such combination to be approved for clinical use. Several issues remain, however, including the precise clinical benefit and toxicity of combination therapy, its effect on drug resistance, and the development of ever more effective therapeutic strategies.

Acquired Immunodeficiency Syndrome↗

Pseudallescheria boydii endocarditis of the pulmonic valve in a liver transplant recipient.

We describe a case of Pseudallescheria boydii endocarditis involving the pulmonic valve in an orthotopic liver transplant recipient. The patient required transplantation because of hepatic failure secondary to chronic active hepatitis B. His postoperative course was complicated by surgery for gastric and duodenal ulcers, persistent fever, and, ultimately, sepsis leading to oliguric renal failure. Two days before death, the patient experienced complete heart block, and an echocardiogram revealed pulmonic valve thickening and an endocardial mass along the left side of the septum. At autopsy the patient was found to have a vegetation on the pulmonic valve and a septal abscess. There were multiple fungal emboli found throughout other organs, and P. boydii was obtained on culture. This unique association between pulmonic valve endocarditis and myocardial septal abscess is discussed. In addition, review of the five previous cases of P. boydii endocarditis reveals that this rare infection is associated with immunosuppression and prosthetic devices.

Endocarditis↗

Didanosine and zidovudine resistance patterns in clinical isolates of human immunodeficiency virus type 1 as determined by a replication endpoint concentration assay.

Reports of in vitro resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine (AZT) have raised concerns about the development of resistance to other dideoxynucleosides in clinical use. To address this, we have developed a screening assay which supports the growth of clinical isolates and have applied this to a series of paired isolates from patients entered into a phase I trial of didanosine (DDI). Thirteen patients (10 with AIDS, 3 with AIDS-related complex) who had been exposed to AZT for a mean of 6.5 months (range, 1 to 13 months) were treated with DDI at 750 mg/day. Paired isolates were obtained pretherapy and after a mean of 58 weeks (range, 21 to 90) of DDI therapy by coculture of peripheral blood mononuclear leukocytes (PBLs) with phytohemagglutinin-stimulated donor PBLs. Isolates were passaged only one additional time in PBLs and then tested in parallel in a microtiter assay with phytohemagglutinin-stimulated donor PBLs as targets. PBLs were infected with 10(5) 50% tissue culture infectious doses per 10(7) cells and exposed to DDI (1 to 50 microM) or AZT (0.01 to 100 microM), and supernatants were assayed for the HIV p24 antigen at 7 days postinfection. Control AZT-susceptible and resistant isolates were included. The median pre- and posttherapy DDI susceptibilities of the 13 pairs of isolates were 10.0 microM (range, 1 to 25 microM) and 17.5 microM (range, 2.5 to 50 microM), respectively (P = 0.036; Wilcoxon signed-rank test). These studies thus indicated that (i) the susceptibility to DDI tends to mildly decrease with drug exposure; (ii) the susceptibility to AZT improves with time off AZT; (iii) baseline susceptibilities to DDI have a wide range, and the CD4 response may correlate with the initial susceptibility; and (iv) a PBL-based microtiter assay is useful for screening clinical isolated for dideoxynucleoside susceptibility profiles.

Didanosine↗