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Biomedical subjects

R C Walker

Publications and source records attributed to R C Walker.

At least 19 recordsLinked to original sources
PubMed1999

The fluoroquinolones.

The quinolones are broad-spectrum antibacterial agents that have a novel mechanism of action. As synthetic compounds, these agents have been developed extensively to optimize antimicrobial activity, pharmacokinetic properties, and drug safety. Although earlier quinolones were effective only in the genitourinary and gastrointestinal tracts and only had activity against aerobic gram-negative bacteria, newer quinolones have wider potential applications and a broader spectrum of activity. Some of the newer quinolones will have a role in the treatment of community-acquired pneumonia and intra-abdominal infections. Ciprofloxacin remains the most potent quinolone against Pseudomonas aeruginosa. Among the quinolones, important differences exist in renal and hepatic elimination and dose-adjustment regimens. Although there are many Food and Drug Administration-approved indications for some of the newer quinolones, the quinolones are the drug of choice for only a few infections. Quinolone-resistant bacteria are being increasingly identified and emerge under selective pressure created by extensive use.

Anti-Infective Agents↗
PubMed1998

Respiratory syncytial virus pneumonitis-induced diffuse alveolar damage in an autologous bone marrow transplant recipient.

A 24-year-old woman with recurrent Hodgkin's lymphoma, stage IIB nodular sclerosing type, underwent an autologous bone marrow transplantation. Forty-five days after transplantation, an upper respiratory tract infection developed that progressed to respiratory distress necessitating mechanical ventilation. An open-lung biopsy demonstrated diffuse alveolar damage. After an extensive search for the cause of the respiratory compromise, we detected respiratory syncytial virus in a bronchoalveolar lavage specimen. The patient was immediately treated with aerosolized ribavirin and intravenous immunoglobulin; her symptoms resolved, and she was extubated 4 days after initiation of therapy.

Adult↗
PubMed1998

Disseminated Kaposi's sarcoma after heart transplantation: association with Kaposi's sarcoma-associated herpesvirus.

BACKGROUND: Kaposi's sarcoma is an endothelial tumor rarely diagnosed after heart transplantation. We report on a patient originally from Africa in whom Kaposi's sarcoma developed in association with Kaposi's sarcoma-associated herpesvirus. METHODS: A man from Ghana had constitutional symptoms associated with multiple pulmonary nodules that developed 3 months after heart transplantation. Kaposi's sarcoma was diagnosed by thorascopic biopsy. Treatment consisted of reducing immunosuppression therapy and adding famciclovir treatment. Symptoms resolved within 1 month after treatment, and no disease progression was observed for 5 months. The patient died suddenly 8 months after heart transplantation; autopsy revealed occlusion of the left anterior descending coronary artery and grade 3A rejection. Extensive Kaposi's sarcoma was observed in the lungs and gastrointestinal tract at autopsy. RESULTS: Pathologic analysis of the tumor demonstrated features consistent with Kaposi's sarcoma. Polymerase chain reaction and in situ hybridization demonstrated the presence of Kaposi's sarcoma-associated herpesvirus. CONCLUSION: Kaposi's sarcoma rarely is diagnosed after transplantation. Patients infected with Kaposi's sarcoma-associated herpesvirus may be at increased risk. Screening for Kaposi's sarcoma-associated herpesvirus may be indicated in patients at risk. The role of antiviral medications and immunization in the treatment and prevention of the disorder is unknown.

2-Aminopurine↗
PubMed1997

Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database.

BACKGROUND: The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. METHODS: One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages. RESULTS: During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS: Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.

Acyclovir↗
PubMed1996

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder.

Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease. We therefore conducted a risk factor analysis of variables that might predict the development of PTLD. Specifically, since EBV may cause both PTLD and the development of monoclonal proteins (M protein), we sought to determine if the development of an M protein preceded and therefore might serve as a predictive marker of subsequent PTLD. Before and after liver transplantation, 201 patients were evaluated for the presence of urine and serum M proteins. Patients were followed to monitor the development of PTLD for a mean of 1,733 days. PTLD developed in seven patients (3.5%), three (43%) of whom died from disseminated PTLD. PTLD was classified as polymorphous in six patients and monomorphous in one patient. Fifty-seven patients (28%) developed an M protein after transplantation: five of seven patients (71%) with PTLD and 52/194 (27%) of patients without PTLD. Multivariate risk factor analysis for the development of an M protein after transplantation identified cytomegalovirus (CMV) donor seropositivity (P = 0.0002) and postoperative symptomatic CMV infection (P = 0.019) as risk factors. Whereas EBV serostatus of either the donor or recipient was not found to be a risk factor for the occurrence of either an M protein or PTLD, the development of a serum immunoglobulin M (IgM) M protein (P = 0.04) and of any urine M protein (P = 0.01) was identified by univariate analysis as being associated with the development of PTLD. Further studies are needed to determine the predictive value of M proteins as a marker for PTLD. Until such time, the development of serum or urine M protein should heighten the suspicion of developing PTLD.

Adolescent↗
PubMed1996

Transmission of invasive aspergillosis from a subclinically infected donor to three different organ transplant recipients.

OBJECTIVE: To describe a cluster of donor-transmitted cases of invasive aspergillosis. DESIGN: Case series of epidemiologically linked cases of invasive aspergillosis. SETTING: Two tertiary care centers with solid-organ transplant programs. PATIENTS: Two kidney recipients, one heart recipient, and the single donor. MEASUREMENTS: Routine clinical, microbiological, and pathologic investigation as dictated for patient care. Epidemiologic analysis to establish linkage among cases. RESULTS: Three allografts (two kidneys and a heart) from a single donor transmitted invasive aspergillosis to the recipients. Three weeks after transplantation, the two kidney recipients had fever and urine cultures positive for Aspergillus fumigatus. The infected kidneys had multiple Aspergillus abscesses and had to be removed to cure the patients. The heart recipient had a negative workup when a diagnosis of aspergillosis was made for the kidney recipients but presented three months later with aspergillus endocarditis with hematogenous spread to the eyes and to the skin. Treatment included eye surgery, aortic valve replacement, and antifungal therapy; control of infection ensued. The donor was intensely immunosuppressed (17 days post-liver transplantation with death from intracerebral bleeding) but had no clinical or autopsy evidence of aspergillosis. Donor tracheal secretions obtained at the time of organ harvest later grew A fumigatus. CONCLUSION: Expanded criteria for organ donation have to be balanced against infectious risk to organ recipients. A fumigatus can be transmitted from a subclinically infected donor to solid-organ transplant recipients.

Abscess↗
PubMed1995

Structure and evolution of the compact radio source in NGC 1275.

Investigations of the fine-scale structure in the compact nucleus of the radio source 3C 84 in NGC 1275 (New General Catalogue number) are reported. Structural monitoring observations beginning as early as 1976, and continuing to the present, revealed subluminal motions in a jet-like relatively diffuse region extending away from a flat-spectrum core. A counterjet feature was discovered in 1993, and very recent nearly simultaneous studies have detected the same feature at five frequencies ranging from 5 to 43 GHz. The counterjet exhibits a strong low-frequency cutoff, giving this region of the source an inverted spectrum. The observations are consistent with a physical model in which the cutoff arises from free-free absorption in a volume that surrounds the core but obscures only the counterjet feature. If such a model is confirmed, very-long-baseline radio interferometry observations can then be used to probe the accretion region, outside the radio jet, on parsec scales.

Journal Article↗
PubMed1995

Pretransplantation assessment of the risk of lymphoproliferative disorder.

Posttransplantation lymphoproliferative disorder (PTLD) is an uncommon but often fatal complication of solid organ transplantation that occurs in approximately 3% of patients. To determine the relative importance and relationship of potential risk factors for PTLD before transplantation (i.e., Epstein-Barr virus [EBV] serostatus of the recipient and the cytomegalovirus [CMV] sero-status of the recipient and the potential donor) and the principal risk factor after transplantation (immunosuppression with antilymphocyte antibody), we analyzed the findings for the first 381 consecutive adult nonrenal transplant recipients seen at Mayo Clinic. In the absence of the other risk factors, the incidence rate of PTLD for EBV-seronegative recipients was 24 times higher (95% confidence interval [CI]: 6.2, 89) than that for EBV-seropositive recipients. The additional risk factors of therapy with OKT3 for rejection and CMV seromismatch (i.e., a negative recipient and a positive donor) each further amplified this risk four- to sixfold. Together, all three risk factors acted synergistically to increase the incidence rate of fatal and/or CNS PTLD by a factor of 654 (CI: 368, 1,162) compared with the low incidence rate (.458 cases per 100 person years) when none of these risk factors were present. Pretransplantation determination of recipient EBV and CMV serostatus can identify a subgroup of patients whose risk for severe PTLD may preclude transplantation.

Adult↗
PubMed1994

Evolving strategies in lung transplantation for emphysema.

Evolving strategies of pulmonary preservation, bronchial revascularization, immunosuppression, and infectious disease management were used in 15 initial consecutive patients undergoing lung transplantation for emphysema. There were 10 women and 5 men with a mean age of 49 years (range, 36 to 60 years). All patients required supplemental oxygen therapy. One bilateral, 9 left, and 5 right transplantations were performed. Mean preoperative forced expiratory volume in 1 second and total lung capacity were 16% and 146%, respectively, of predicted. Quadruple drug immunosuppression was used. Actuarial 1-year survival in this initial series is 93.3% +/- 6.4% (Kaplan-Meier) with one early cardiac death at day 71. Mean forced expiratory volume in 1 second and diffusing capacity for carbon monoxide at discharge were 43% and 62%, respectively, of predicted. Rehabilitation has been excellent, and all survivors are active and free of supplemental oxygen. During the study, the following treatment strategies have evolved: (1) University of Wisconsin solution has replaced Euro-Collins' solution for pulmonary preservation; (2) direct bronchial revascularization with the internal thoracic artery now is used; (3) an algorithm-based variable dose OKT3 induction regimen has resulted in a major reduction in dosage; and (4) infectious disease management focuses on the prophylaxis of cytomegalovirus and fungal infection using prolonged ganciclovir and early itraconazole therapy as well as the avoidance of Epstein-Barr virus mismatches. Single-lung transplantation for emphysema has excellent early results with continuing evolving management strategies.

Adenosine↗
PubMed1992

Strategies for prevention of infection after cardiac transplantation.

Infection remains a major cause of morbidity and mortality after cardiac transplantation. Most infections occur during the first few months after transplantation. Although late infection does occur, the risk of infection during maintenance immunosuppression is low in the absence of recurrent rejection that necessitates augmentation of suppression of the immune response. Before cardiac transplantation, the risk factors for infectious disease in potential candidates should be assessed. A detailed history of past infections should be elicited, and patients should be screened for the presence of active indolent infection. In addition, potential donors must be thoroughly assessed for organ-transmittable infection. Many common infections that may occur after cardiac transplantation can be prevented with the use of appropriate prophylactic regimens directed toward cytomegalovirus, Toxoplasma gondii, Pneumocystis carinii, and herpes simplex virus. Periodic surveillance serologic tests and cultures after cardiac transplantation facilitate early diagnosis and prompt institution of appropriate therapy.

Heart Transplantation↗
PubMed1991

Granulomatous hepatitis: a retrospective review of 88 cases at the Mayo Clinic.

Although several studies have shown that sarcoidosis and tuberculosis are the most common causes of granulomatous hepatitis (GH), these studies were biased because results of unselected liver biopsies and autopsy reports were included. We reviewed the medical records of patients diagnosed with GH at the Mayo Clinic between September 1976 and October 1985 for the current study. Our study group consisted of 45 women and 43 men (mean age, 54.2 years). Overall, 65 patients (74%) were symptomatic; the rest had only liver enzyme abnormalities. The mean duration of symptoms was 19.1 months. Assessment of these patients and a comprehensive workup for infectious agents or other causes revealed idiopathic GH confined to the liver in 50%, sarcoidosis with confirmed extrahepatic disease in 22%, drug-related GH in 6%, tuberculosis in 3%, and other causes in 19%. Our study found a much higher frequency of idiopathic GH than previously published reports, and it represents the largest number of cases of idiopathic liver granulomas reported in a single series.

Biopsy↗
PubMed1991

The fluoroquinolones.

The fluoroquinolone class of antibiotics promises to become as diverse and as important as beta-lactam agents. The fluoroquinolones inhibit bacterial DNA gyrase and are bactericidal. All fluoroquinolones have potent activity against most gram-negative bacteria; ciprofloxacin is the most active against Pseudomonas aeruginosa. Activity against gram-positive organisms is variable; methicillin-resistant Staphylococcus aureus has acquired resistance to the fluoroquinolones at an alarming rate. Currently available quinolones do not have, but new quinolone agents likely will have, substantial activity against anaerobic bacteria. Some quinolones are also active against Mycobacterium, Chlamydia, and Mycoplasma organisms. All fluoroquinolones have excellent absorption after oral administration; however, this process can be impaired by the presence of aluminum- or magnesium-containing antacids and by zinc, iron, or calcium supplements. Ciprofloxacin is also available for intravenous use. Although most fluoroquinolones do not achieve adequate cerebrospinal fluid levels, penetration into other tissues is excellent. Dosage adjustments for renal and hepatic dysfunction vary among the quinolones. Although side effects are rare, concomitant use of caffeine or theophylline with some quinolones may cause toxicity to the central nervous system. Because they may affect the development of cartilage, all fluoroquinolones are contraindicated in children, adolescents, and pregnant or breast-feeding women.

4-Quinolones↗
PubMed1991

The role of the clinical microbiology laboratory in transplantation.

The clinical microbiology laboratory plays a central role in any transplantation program. Pretransplantation microbiologic testing often determines prophylactic treatment, donor selection, and blood product use. With suspected infection, rapid microbiologic tests permit prompt therapy but are challenged by an ever-changing diversity of potential pathogens and limited specimen size. Antigen detection and the polymerase chain reaction with nucleic acid hybridization are newer methods that promise earlier detection of such serious infections as disseminated aspergillosis and primary cytomegalovirus and may reveal new microbial causes of various posttransplantation syndromes.

Humans↗
PubMed1990

Effect of lithium carbonate on mouse and rat embryos in vitro.

Lithium is effective in the treatment of manic-depressive psychosis but is suspected to be a developmental toxicant in humans. It is a developmental toxicant in mice and rats in vivo, but at human therapeutic serum levels of 0.6-1.6 meq/L, rats appear to be more sensitive to the effects of the drug than do mice. The species susceptibility to lithium-induced defects was evaluated by using a rodent whole embryo culture system employing mouse and rat embryos treated at comparable developmental stages. Mouse embryos were cultured on gestational days 8-10, and rat embryos were cultured on gestational days 10-12. Care was taken to insure that all embryos had 10 +/- 2 somite pairs at the beginning of the culture period. Embryos were cultured for 44 hours in rat serum to which lithium was added to attain final drug concentrations of 0.6, 1.2, 1.8, 2.4, or 5.0 meq/L. Control embryos were treated with distilled water, which served as the vehicle. In rats, lithium induced significant decreases in various parameters at 1.8, 2.4, and 5.0 meq/L; no malformations were observed in rats of this stage. In mice, significant decreases occurred at 2.4 and 5.0 meq/L, and embryos treated at the highest concentration had a significantly increased frequency of open neural tubes. Rat embryos were also cultured with lithium on gestational days 9-11. The lowest dose producing developmental toxicity at this stage was 0.6 meq/L. Open neural tubes were present among younger rat embryos; however, this defect occurred in all groups, including the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗