Influenza infection in patients before and after liver transplantation.

Infection with influenza virus poses specific problems in pediatric and adult liver transplant recipients, both before and after liver transplantation. These include a higher rate of pulmonary and extrapulmonary complications, development of rejection with graft dysfunction, prolonged shedding of influenza virus, and increased drug-resistance. Hepatic decompensation may occur during influenza infection in patients with cirrhosis. Current prophylaxis includes yearly vaccination with trivalent inactivated vaccine. Appropriate diagnosis and prompt treatment of any upper respiratory infections are indicated in these patients. In this review, we describe a case of influenza viral pneumonia in an adult liver transplant recipient, review basic and clinical aspects of influenza infection in this patient population, and discuss current modes of prevention and treatment in detail.

Orthopaedic infections.

Patients with orthopaedic infections may require admission to the intensive care unit (ICU). Necrotizing fasciitis and clostridial myonecrosis (gas gangrene) are serious soft tissue infections that may cause life-threatening complications. Patients suffering from infectious arthritis, osteomyelitis, or prosthetic joint infections may be seen in the ICU as a result of a previous injury, surgery, or delayed infectious processes. This article introduces the ICU nurse to the pathophysiology, clinical presentation, and management of a variety of orthopaedic infections.

Expediting the early hospital care of the adult patient with nontraumatic chest pain: impact of a modified ED triage protocol.

A prospective study that compared a traditional emergency department (ED) triage protocol with an expedited protocol was conducted to determine if minimizing the subjectivity of nursing triage would result in more efficient management of adult patients presenting with nontraumatic chest pain. The traditional protocol triaged 382 patients into 1 of 5 categories of acuity. The expedited study group (418 patients) were triaged as usual but subsequently were treated as if they were triage category 1 or 2 (medical evaluation within 15 minutes of arrival). Traditional triage led to 40% of acute myocardial infarction (AMI) patients being triaged into inappropriately low-acuity categories. The expedited protocol resulted in significant improvement in the following intervals: ED arrival to triage, triage to cubicle, ED arrival to cubicle, ED arrival to electrocardiogram (ECG) ordered, ED arrival to ECG available, ED arrival to physician evaluation, and ED arrival to decision to thrombolyse. Study patients with non-AMI cardiac chest pain and AMI cardiac chest pain were evaluated by a physician an average of 12 minutes and 8 minutes after ED arrival, respectively. Delays in interdepartmental processes, such as ECG-technician responsiveness, thrombolysis protocol fulfillment and thrombolytic agent delivery, negated benefits derived from improvements in internal processes. Effective coordination of the numerous processes involved in the initial ED management of adult patients with nontraumatic chest pain is required to make thrombolytic therapy for AMI within 30 minutes of patient arrival a routinely achievable goal.

Waldenström's macroglobulinemia: long-term results with the M-2 protocol.

Thirty-three patients with symptomatic Waldenström's macroglobulinemia have been treated with the M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Therapy was administered every 5 weeks for 2 years and every 10 weeks for an additional 1-3 years. Median clinical and laboratory parameters included age 70 years (range 52-87), performance status 1 (1-3), prior therapy 7, weight loss 12, symptomatic hyperviscosity 13, splenomegaly 22, lymphadenopathy 7, hemoglobin 9.6 g/dl (6.7-14.6), IgM paraprotein level 2000 mg% (340-11,600), and serum viscosity 2.1 (1.4-6.0). Responses were observed in 27 patients, of whom 21 were partial responses. Survival ranges from 1 to 120+ months with 58% of patients projected to be alive at 10 years. Twenty-one patients remain alive, of whom 10 are greater than or equal to 6 years from initiation of therapy with M-2. Treatment has been well tolerated with usually only mild to moderate hematologic toxicity. Median nadir white blood cells during the first cycle was 3000/mm3 (1000-5500). Peripheral neuropathy was seen in 54% secondary to vincristine. Nausea/vomiting, anemia requiring transfusions, and alopecia were each noted in approximately 25% of patients. Sepsis was observed in 2 patients. Two characteristics, age and prior therapy, were found to be of borderline statistical significance (p = 0.03) using univariate analysis but were not significant with multivariate analysis. The M-2 protocol may be able to produce prolonged survival in the majority of patients with Waldenström's macroglobulinemia. Additional trials are needed to develop recommendations for therapy as well as factors predictive for survival and suitability for treatment.

Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection.

One hundred nineteen patients with primary and 31 patients with nonprimary first-episode genital herpes were treated for ten days with 200 mg of acyclovir capsules or placebo capsules orally five times daily. Among acyclovir recipients with primary genital herpes, the median duration of viral shedding (two days), time to crusting of all lesions (seven days), time to healing of all lesions (12 days), and duration of local pain (five days) and constitutional symptoms (three days) were shorter than among placebo recipients (9, 10, 16, 7, and 6 days, respectively). Among patients with nonprimary first-episode genital herpes, oral acyclovir shortened the median duration of viral shedding but had no significant effect on the duration of lesions or symptoms. The time to first recurrence and frequency of recurrences were similar in acyclovir- and placebo-treated patients. Oral acyclovir treatment of primary first-episode genital herpes shortens the duration of viral shedding and symptoms and accelerates healing, but it does not appear to influence subsequent genital recurrences.

Treatment of recurrent genital herpes simplex infections with oral acyclovir. A controlled trial.

Two hundred fifty patients were entered into a multicenter trial to evaluate the efficacy and toxicity of orally administered acyclovir for treatment of recurrent genital herpes. The study consisted of part A, in which patients entered the study within 48 hours of the onset of lesions, and part B, in which patients self-initiated therapy as soon as possible after the onset of a recurrent episode. In both parts, patients received either acyclovir (200 mg) or placebo, five times daily for five days. In both parts, the duration of virus shedding and the time to crusting and healing of lesions were shorter among acyclovir recipients than among placebo recipients. In part B, fewer acyclovir recipients formed new lesions during the study medication period than did placebo recipients. When parts A and B were compared directly, the duration of virus shedding and the times required for crusting and healing of lesions were significantly shorter among acyclovir recipients in part B than among acyclovir recipients in part A. No significant differences in the duration of itching and pain or in the times of subsequent recurrence were noted between acyclovir and placebo groups in either part A or part B. No significant toxic or adverse reactions were seen in acyclovir recipients. Oral acyclovir shortens the duration of virus shedding and the duration of lesions in patients with recurrent genital herpes. These effects are more pronounced when therapy is self-initiated by patients early in the course of a recurrent episode.

Rapid viral diagnosis.

The advent of antiviral chemotherapy provides a strong impetus to develop methods to diagnose viral infections rapidly and accurately. Several other potential contributions of rapid viral diagnoses to patient management also exist. Virus isolation remains the "gold standard" of viral diagnosis against which most newly developed diagnostic approaches--including serologic testing, viral-enzyme detection, microscopic techniques, radioimmunoassays, and enzyme immunoassays--must be compared. Since, as currently performed, enzyme immunoassays such as enzyme-linked immunosorbent assays have reached the limit of their sensitivity, fully satisfactory rapid viral diagnosis will require new approaches. Two such potentially useful approaches are the detection of viral antigen with a method that permits visual localization of virus-specific immunoenzymatic staining and the detection of viral nucleic acids in clinical specimens by hybridization with nucleic-acid probes.

Detection of herpes simplex virus in clinical specimens by DNA hybridization.

An assay to detect herpes simplex virus (HSV) DNA in clinical specimens has been developed. It utilizes nucleic acid hybridization with a 32P-labeled DNA probe prepared from a fragment of HSV DNA cloned in a plasmid vector. This assay can detect 5 X 10(4) plaque-forming units of cell-free HSV and as few as four virus-infected cells. The assay has a sensitivity of 78% and a specificity of 100% compared to virus culture for the detection of HSV in swab specimens from genital lesions. No hybridization is observed with uninfected, varicella-zoster virus infected, or cytomegalovirus infected cells, and specimens from herpes zoster lesions are uniformly negative. While hybridization with a 32P-labeled probe is not optimally suited for routine diagnostic use, this report establishes the feasibility of using nucleic acid hybridization to detect HSV in clinical specimens.

Enzyme immunofiltration technique for rapid diagnosis of herpes simplex virus eye infections in a rabbit model.

A rapid enzyme immunofiltration assay for herpes simplex virus (HSV) has been developed which is sensitive enough to detect viral antigens in eye swabs from rabbits with primary herpes keratitis. This assay employs a specially designed filter manifold to immobilize whole cells and cell debris dissociated from the swabs. Viral antigens trapped on the filters are then detected in an indirect immunoassay utilizing staphylococcal protein A conjugated with horseradish peroxidase. The assay required only 2.5 h to perform and could be read visually. Reconstruction experiments indicated that antigen from as few as 49 HSV-infected cells could be detected. Calcium alginate swabs were shown to recover more viral antigen than dacron swabs. The enzyme immunofiltration assay detected HSV antigens on 95% of the eye swabs from which infectious virus was recovered. In addition, HSV antigen was also detected in several swabs from infected eyes which did not yield infectious virus, presumably because the virus was neutralized by native antibody present in the lacrimal fluid. This enzyme immunofiltration assay technique lends itself to the elution of native antibody bound to the viral antigens, and this may be especially applicable in the diagnosis of recurrent HSV keratitis, where antiviral antibody in the lacrimal fluid may interfere with virus isolation and fluorescent-antibody or other virus detection assays.

Controlled trial of oral acyclovir in the therapy of recurrent herpes simplex genitalis. A preliminary report.

A randomized, placebo-controlled, double-blind study was performed to evaluate the efficacy and toxicity of orally administered acyclovir in the treatment of patients with recurrent herpes simplex genitalis (HSG). A total of 107 patients from centers in Burlington, Vermont, and San Diego, California, were entered into the study within 48 hours of the onset of lesions. Patients who received acyclovir shed virus for 1.8 +/- 0.6 days (mean +/- SEM) compared with 2.8 +/- 1.2 days for those who received placebo. The duration of shedding from genital lesions of patients in the acyclovir-treated group was significantly less than from lesions of patients who received placebo (p = 0.016 by a logrank test). An analysis of the toxicity of the drug was performed in 52 of the study participants. Acyclovir was well-tolerated and no alterations were observed in measurements of bone marrow, liver, or kidney function. Orally administered acyclovir is a promising antiviral compound for the treatment of recurrent HSG.

Antibiotic treatment of acute shigellosis: failure of cefamandole compared with trimethoprim/ sulfamethoxazole and ampicillin.

Intravenously administered ampicillin (AMP), trimethoprim-sulfamethoxazole (TMP-SMX) and cefamandole (CEF) were evaluated in 30 children with shigellosis: 11 children received AMP, 10 TMP-SMX, and 9 CEF for a maximum of five days. Discharge criteria included; afebrile greater than 12 hrs, less than 9 stools/day, absence of seizures, and adequate oral intake. AMP or TMP-SMX patients required significantly fewer median days to meet discharge criteria than those who received CEF. AMP and TMP-SMX patients had fewer median days with fever (one day each) compared with CEF (five days). On day five, 7 of 8 CEF, 3 of 10 AMP and 2 of 9 TMP-SMX treated patients remained culture positive. Inhibitory concentrations against all Shigella isolates from CEF patients all were less than or equal to 0.4 microgram CEF/ml. Intravenous TMP-SMX was equivalent to AMP in treatment of children with shigellosis, while CEF was ineffective despite in vitro activity. Clinical and bacteriologic responses were achieved with AMP and TMP-SMX in the majority of patients with less than 5 days of intravenous therapy.

Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells.

Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays.

Use of trained mothers to teach interviewing skills to first-year medical students: a follow-up study.

This report describes an attempt to evaluate the effectiveness of "trained mother" interviews early in the medical school curriculum. As an adjunct to a first-year course that teaches interviewing techniques, half of the students were exposed to an interview with one of three trained mothers early in the course. This treatment interview was immediately followed by a feedback session which concentrated on the content and process of interviewing. At the end of the course, all students had an evaluative interview. Those students who had an initial interview and feedback session with a trained mother scored significantly higher on both the content and process of their interviews than the control group. This technique is an effective and efficient way to teach interviewing skills to medical students prior to entering any of their clinical clerkships. A follow-up assessment conducted one year later indicated that one interview with a trained mother is sufficient for optimal learning and that the skills learned are retained over at least that period of time.

The use of paraprofessionals to teach interviewing skills.

Two nonphysician mothers were each trained to give a consistent and authentic history of a child's common medical problem. At the beginning of a Pediatric Clerkship, one half the students were randomly assigned to interview one of the trained mothers. The interviews were videotaped and then replayed in an evaluative feedback session with each student. At the end of the clerkship these students were rated significantly higher on the process of interviewing than those students who did not have the initial evaluative feedback session.